| + |
PRKACA |
phosphorylation
|
CCND1 |
0.338 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250346 |
Ser234 |
YRLTRFLsRVIKCDP |
in vitro |
|
| pmid |
sentence |
| 8058338 |
PKA phosphorylates three distinct serine residues in cyclin D1 at positions 90, 197 and 234. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250347 |
Ser90 |
NYLDRFLsLEPVKKS |
in vitro |
|
| pmid |
sentence |
| 8058338 |
PKA phosphorylates three distinct serine residues in cyclin D1 at positions 90, 197 and 234. |
|
| Publications: |
2 |
Organism: |
In Vitro |
| + |
GSK3B | down-regulates quantity by destabilization 
phosphorylation
|
CCND1 |
0.776 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-245437 |
Thr286 |
EEVDLACtPTDVRDV |
Homo sapiens |
|
| pmid |
sentence |
| 23552696 |
Active AKT, a common mediator of cell survival signals induced by radiation through multiple intracellular signaling pathways,11, 12 suppresses apoptosis. AKT positively regulates cyclin D1 expression through inactivation of glycogen synthase kinase 3_ (GSK3_). The AKT-mediated phosphorylation of glycogen synthase kinase 3_ on serine9 decreases its kinase activity for Thr286 of cyclin D1, which inhibits the nuclear export and the cytoplasmic proteasomal degradation of cyclin D1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, AML_TRIPLETS, Triple mutant AML |
| + |
GSK3B | down-regulates
phosphorylation
|
CCND1 |
0.776 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-62265 |
Thr286 |
EEVDLACtPTDVRDV |
Homo sapiens |
|
| pmid |
sentence |
| 9832503 |
Phosphorylation of cyclin d1 on a single threonine residue near the carboxyl terminus (thr-286) positively regulates proteasomal degradation of d1. Now, we demonstrate that glycogen synthase kinase-3beta (gsk-3beta) phosphorylates cyclin d1 specifically on thr-286, thereby triggering rapid cyclin d1 turnover now, we demonstrate that glycogen synthase kinase-3beta (gsk-3beta) phosphorylates cyclin d1 specifically on thr-286, thereby triggering rapid cyclin d1 turnover. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-144818 |
Thr286 |
EEVDLACtPTDVRDV |
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 16504004 |
Phosphorylation of cyclin d1 on a single threonine residue near the carboxyl terminus (thr-286) positively regulates proteasomal degradation of d1. Now, we demonstrate that glycogen synthase kinase-3beta (gsk-3beta) phosphorylates cyclin d1 specifically on thr-286, thereby triggering rapid cyclin d1 turnover now, we demonstrate that glycogen synthase kinase-3beta (gsk-3beta) phosphorylates cyclin d1 specifically on thr-286, thereby triggering rapid cyclin d1 turnover. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, AML_TRIPLETS, Triple mutant AML |
| + |
CHUK | down-regulates
phosphorylation
|
CCND1 |
0.389 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-139570 |
Thr286 |
EEVDLACtPTDVRDV |
Homo sapiens |
|
| pmid |
sentence |
| 16103118 |
Ikkalpha regulates subcellular localization and proteolysis of cyclin d1 by phosphorylation of cyclin d1 at thr286. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DYRK1A | down-regulates
phosphorylation
|
CCND1 |
0.406 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-202838 |
Thr286 |
EEVDLACtPTDVRDV |
Homo sapiens |
|
| pmid |
sentence |
| 24119401 |
Dyrk1a controls the rate of cycd1 degradation by directly phosphorylating cycd1 at thr 286 and thereby regulates the fraction of cycling cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DYRK1B | down-regulates
phosphorylation
|
CCND1 |
0.422 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-150126 |
Thr288 |
VDLACTPtDVRDVDI |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 17046823 |
Further, we found that not only gsk-3beta but also dyrk1b modulates cyclin d1 subcellular localization by the phosphorylation of thr(288). These results suggest that dif-3 induces degradation of cyclin d1 through the gsk-3beta- and dyrk1b-mediated threonine phosphorylation in hela cells |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235801 |
Thr288 |
VDLACTPtDVRDVDI |
Mus musculus |
C2C12 Cell, Myoblast |
| pmid |
sentence |
| 15546868 |
Mirk activated mef2 not through direct phosphorylation of mef2 but by phosphorylation of its inhibitors, the class ii histone deacetylases (hdacs). Mef2 is sequestered by class ii hdacs such as hdac5 and mef2-interacting transcriptional repressor (mitr). Mirk antagonized the inhibition of mef2c by mitr, whereas kinase-inactive mirk was ineffective. Mirk phosphorylates class ii hdacs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent manner |
|
| Publications: |
2 |
Organism: |
Homo Sapiens, Mus Musculus |
| Tissue: |
Muscle, Skeletal Muscle |
| + |
CCND1 | up-regulates 
binding
|
HDAC3 |
0.421 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-134056 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15713663 |
Collectively, these studies suggest an important role of cyclin d1 in regulation of ppargamma-mediated adipocyte differentiation through recruitment of hdacs to regulate ppar response element local chromatin structure and ppargamma function. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK14 | up-regulates
phosphorylation
|
CCND1 |
0.439 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-166594 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20626350 |
A large number of cytosolic proteins can be phosphorylated by p38 mapks, including phospholipase a2, the microtubule-associated protein tau, nhe-1, cyclin d1, cdk inhibitors, bcl2 family proteins, growth factor receptors or keratins |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
IMPDH2 | up-regulates quantity by expression 
transcriptional regulation
|
CCND1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260957 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 30518405 |
We further demonstrated that IMPDH2 overexpression accelerated G1/S phase cell cycle transition by inducing increased expression of cyclin D1 and Ki-67 and downregulation of p21Cip1 and p27Kip1. More importantly, G1/S phase cell cycle transition was triggered by IMPDH2 through activation of AKT activity, downregulation of mTOR and FOXO1 transcriptional activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CCND1 | up-regulates
binding
|
CDK4 |
0.964 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-32295 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 7736585 |
D-type cyclins (cyclin d1, d2, or d3) and their associated cyclin-dependent kinases (cdk4, cdk6) connect signals from cytokines to the cell cycle machinery, and they propel cells through the g1 restriction point and into the s phase when activated by cyclin d1, cdk4 is able to phosphorylate prb, |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-201666 |
|
|
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 23562856 |
D-type cyclins (cyclin d1, d2, or d3) and their associated cyclin-dependent kinases (cdk4, cdk6) connect signals from cytokines to the cell cycle machinery, and they propel cells through the g1 restriction point and into the s phase when activated by cyclin d1, cdk4 is able to phosphorylate prb, |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
GLI3 | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.575 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-188878 |
|
|
Homo sapiens |
Breast Cancer Cell, Lung Cancer Cell |
| pmid |
sentence |
| 19860666 |
Gli activators bind to gaccaccca motif to regulate transcription of gli1, ptch1, ptch2, hhip1, mycn, ccnd1, ccnd2, bcl2, cflar, foxf1, foxl1, prdm1 (blimp1), jag2, grem1, and follistatin. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-154234 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17419683 |
Gli activators bind to gaccaccca motif to regulate transcription of gli1, ptch1, ptch2, hhip1, mycn, ccnd1, ccnd2, bcl2, cflar, foxf1, foxl1, prdm1 (blimp1), jag2, grem1, and follistatin. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
CCND1 | form complex 
binding
|
CyclinD1/CDK6 |
0.95 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250680 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 8114739 |
Here, we show that the human PLSTIRE gene product is a novel cyclin-dependent kinase, cdk6. The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
R547 | down-regulates
chemical inhibition
|
CCND1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-206352 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
palbociclib | down-regulates
chemical inhibition
|
CCND1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-189693 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
GH1 | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261629 |
|
|
Homo sapiens |
MCF-10A Cell |
| pmid |
sentence |
| 15665309 |
Autocrine hGH increased the transcription and subsequent mRNA level and protein expression of c-Myc, Cyclin D1, and Bcl-2 in human mammary epithelial cells |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
HACE1 | down-regulates quantity by destabilization
ubiquitination
|
CCND1 |
0.313 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271405 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17694067 |
Mechanistically, the tumor-suppressor function of HACE1 is dependent on its E3 ligase activity and HACE1 controls adhesion-dependent growth and cell cycle progression during cell stress through degradation of cyclin D1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
GLI1/GLI2 | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.549 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269213 |
|
|
Homo sapiens |
PANC-1 Cell |
| pmid |
sentence |
| 32766732 |
GLI1 and GLI2 were shown to co-immunoprecipitate in PANC1 pancreatic cancer cells and RMS13 rhabdomyosarcoma cells.|Chromatin immunoprecipitation showed that GLI1 and GLI2 occupied the same regions at the BCL2, MYCN and CCND1 promoters. Furthermore, depletion of GLI1 inhibited GLI2 occupancy at these promoters, suggesting that GLI1/GLI2 interaction is required for the recruitment of GLI2 to these sites. | RNAi knockdown of either GLI1 or GLI2 inhibited expression of many well-characterized GLI target genes (BCL2, MYCN, PTCH2, IL7 and CCND1) in PANC1 cells |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CTNNB1 | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.794 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-134216 |
|
|
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 15735151 |
Activated dvl binds and inhibits the phosphorylation of beta catenin by gsk3beta/alfa, blocking beta catenin degradation (fig 2?2),), so that beta catenin accumulates and translocates to the nucleus, where it interacts with the t cell specific factor (tcf)/lymphoid enhancer binding factor 1 (lef-1) transcription factor and induces the transcription of target genes such as c-jun, c-myc, and cyclin d1 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-98379 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12589056 |
The resulting accumulation of beta-catenin leads to its nuclear translocation and binding to tcf/lef transcription factors to induce target genes including cyclin d1. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia |
| + |
TEAD1 | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.275 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235849 |
|
|
Mus musculus |
C2C12 Cell, Myoblast |
| pmid |
sentence |
| 20153295 |
We found that the expression of myf5 and cyclind1 remained significantly elevated upon induction of differentiation in cells that were overexpressing hyap1 s127a compared to cells transfected with wildtype hyap and empty vector;yap directly induced the transcription of ccnd1 and foxm1, in cooperation with tead transcription factor. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-195534 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22286761 |
Yap directly induced the transcription of ccnd1 and foxm1, in cooperation with tead transcription factor. |
|
| Publications: |
2 |
Organism: |
Mus Musculus, Homo Sapiens |
| Tissue: |
Muscle, Skeletal Muscle, Myotube |
| + |
ESR1 | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.746 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-135053 |
|
|
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 15808510 |
Ikkalpha in conjunction with eralpha and aib1/src-3, is important in activating the transcription of estrogen-responsive genes, including cyclin d1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NCOA3 | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.489 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-135056 |
|
|
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 15808510 |
Ikkalpha in conjunction with eralpha and aib1/src-3, is important in activating the transcription of estrogen-responsive genes, including cyclin d1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CCND1 | form complex
binding
|
CyclinD/CDK4 |
0.964 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-32298 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 7736585 |
D-type cyclins (cyclin d1, d2, or d3) and their associated cyclin-dependent kinases (cdk4, cdk6) connect signals from cytokines to the cell cycle machinery, and they propel cells through the g1 restriction point and into the s phase when activated by cyclin d1, cdk4 is able to phosphorylate prb, |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SWI/SNF complex | down-regulates quantity by repression 
transcriptional regulation
|
CCND1 |
0.481 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256293 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12138206 |
INI1/hSNF5 is a component of the ATP-dependent chromatin remodeling hSWI/SNF complex [.]. Our data suggest that one of the mechanisms by which INI1/hSNF5 exerts its tumor suppressor function is by mediating the cell cycle arrest due to the direct recruitment of HDAC activity to the cyclin D1 promoter thereby causing its repression and G(0)-G(1) arrest. These results together indicate that cyclin D1 is a direct target for repression by INI1/hSNF5. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
HDAC1 | up-regulates
binding
|
CCND1 |
0.685 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-134059 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15713663 |
Cyclin d1 bound hdac in vivo and preferentially physically associated with hdac1, hdac2, hdac3, and hdac5. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
HDAC2 | up-regulates
binding
|
CCND1 |
0.482 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-134062 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15713663 |
Cyclin d1 bound hdac in vivo and preferentially physically associated with hdac1, hdac2, hdac3, and hdac5. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
4-(2,6-dichlorobenzamido)-N-(piperidin-4-yl)-pyrazole-3-carboxamide | down-regulates
chemical inhibition
|
CCND1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-189972 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MYCT1 | down-regulates quantity by repression
transcriptional regulation
|
CCND1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261730 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 30283340 |
MYCT1 overexpression significantly inhibited cell proliferation, arrested cell cycle at G0/G1 phase, and downregulated the expression of cyclins D and E. Moreover, MYCT1 overexpression triggered apoptosis in AML cells, which was accompanied by enhanced cleavage of caspase-3 and -9, upregulated expression of B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), and downregulated Bcl-2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK14 | down-regulates quantity by repression
transcriptional regulation
|
CCND1 |
0.439 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-43096 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 8702807 |
This result suggests that the p38mapk cascade could be involved in the negative regulation of cyclin d1 transcription and thus antagonize the mitogen-dependent stimulation of cyclin d1 transcription mediated, at least in part, by the p42/p44mapk cascade. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CCND1 | up-regulates
binding
|
HDAC2 |
0.482 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-134053 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15713663 |
Cyclin d1 bound hdac in vivo and preferentially physically associated with hdac1, hdac2, hdac3, and hdac5. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CCND1 | down-regulates activity
|
Adipogenesis |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258981 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15713663 |
Collectively, these studies suggest an important role of cyclin D1 in regulation of PPARgamma-mediated adipocyte differentiation through recruitment of HDACs to regulate PPAR response element local chromatin structure and PPARgamma function. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FBXW8 | down-regulates quantity by destabilization
binding
|
CCND1 |
0.526 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271624 |
|
|
Homo sapiens |
HCT-116 Cell |
| pmid |
sentence |
| 17205132 |
We next investigated whether in vitro ubiquitination of cyclin D1 through the SCF-like (SCFL) complex FBXW8 (SKP1-CUL7-FBXW8-RBX1/SCFLFBXW8) requires phosphorylation of cyclin D1 at Thr286 (Fig. 3F). Polyubiquitination through SCFLFBXW8 was dramatically reduced by the depletion of ERK2 (lane 2). Furthermore, cyclin D1 polyubiquitination was largely prevented by the alanine-for-Thr286 substitution (T286A, lane 3), suggesting that phosphorylation of cyclin D1 at Thr286 is necessary for ubiquitination by SCFLFBXW8. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SKP2 | down-regulates quantity by destabilization
binding
|
CCND1 |
0.578 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272575 |
|
|
Homo sapiens |
SK-UT-1B Cell |
| pmid |
sentence |
| 11439327 |
We show that SK-UT-1B cells express a novel splice variant of Skp2 that localizes to the cytoplasm and that cyclin D1 ubiquitination takes place in the nucleus. We propose that the translocation of Skp2 into the nucleus is required for the ubiquitination of cyclin D1 and that the absence of the SCF(Skp2) complex in the nucleus of SK-UT-1B cells is the mechanism underlying the ubiquitination defect observed in this cell line. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CTNNB1 | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.794 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277738 |
|
|
Homo sapiens |
PANC-1 Cell |
| pmid |
sentence |
| 30519351 |
One of the most well studied activators of CCND1 transcription is β-catenin, which could be actived by AKT signalling to inducing G1/S transition. When β-catenin is translocated from the cytoplasm to the nucleus, it forms a complex with the ternary complex factor (TCF) and/or lymphoid enhancer-binding factor (LEF) and stimulates cyclin D1 gene transcription (Fig. 4C).In agreement with the data described above, a chromatin immunoprecipitation (ChIP) assay confirmed that TNC regulates the binding of β-catenin to the TCF/LEF-binding site in the CCND1 promoter (Fig. 4C). Additionally, the β-cateninbinding activity with respect to the CCND1 promoter was much higher in TNC-overexpression PANC-1 cells than in the vector controls. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia |
| + |
TCF4 | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.347 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255388 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20459685 |
Cd2+ reduced the interaction of beta-catenin with AJ components (E-cadherin, alpha-catenin) and increased binding to the transcription factor TCF4 of the Wnt pathway, which was upregulated and translocated to the nucleus. While Wnt target genes (c-Myc, cyclin D1 and ABCB1) were up-regulated by Cd2+, electromobility shift assays showed increased TCF4 binding to cyclin D1 and ABCB1 promoter sequences with Cd2+. Overexpression of wild-type and mutant TCF4 confirmed Cd2+-induced Wnt signaling. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CCND1 | up-regulates
|
Proliferation |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255412 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18177723 |
Cyclin D1 is necessary for proliferation of different cell types, including myogenic cells. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260014 |
|
|
Homo sapiens |
Hepatocyte |
| pmid |
sentence |
| 11731443 |
Cyclin D1 regulates mitogen-dependent progression through G1 phase in cultured cells, and its overexpression in malignant cells is thought to contribute to autonomous proliferation in vivo. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, DNMT3A in AML, AML_TRIPLETS, Triple mutant AML |
| + |
MYC | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.512 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-102731 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12835716 |
C-myc directly activates transcription of cyclin d1, cyclin d2 and cdk4, and leads to cdk 4/6 activation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, DNMT3A in AML, AML_TRIPLETS, Triple mutant AML |
| + |
NfKb-p65/p50 | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.483 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235648 |
|
|
Mus musculus |
C2C12 Cell, Myoblast |
| pmid |
sentence |
| 10409765 |
Nf-kappab regulation of cyclin d1 occurs at the transcriptional level and is mediated by direct binding of nf-kappab to multiple sites in the cyclin d1 promoter. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Tissue: |
Muscle, Skeletal Muscle |
| Pathways: | Acute Myeloid Leukemia |
| + |
DNMT3A | down-regulates quantity by repression
transcriptional regulation
|
CCND1 |
0.485 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255808 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19786833 |
Based on one of these publications, we here showed that the interaction of Dnmt3a with c-myc promote the specific methylation of CG dinucleotides localized in c-myc boxes of promoter regions of CDKN2a, CCND1 and TIMP2 genes. Acellular experiments corroborated and complemented these results by revealing that the specificity of consensus sequence for DNA methylation of Dnmt3a is increased in presence of c-myc. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, DNMT3A in AML, AML_TRIPLETS, Triple mutant AML |
| + |
SRPK2 | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-186763 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19592491 |
Compared with control, srpk2 wild type evidently elevated cyclin d1 transcription, and the catalytic activity was lost in srpk2 kd, suggesting that kinase activity of srpk2 is required for this effect. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 1-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
CCND1 |
0.532 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272577 |
|
|
Homo sapiens |
SK-UT-1B Cell |
| pmid |
sentence |
| 11439327 |
We show that SK-UT-1B cells express a novel splice variant of Skp2 that localizes to the cytoplasm and that cyclin D1 ubiquitination takes place in the nucleus. We propose that the translocation of Skp2 into the nucleus is required for the ubiquitination of cyclin D1 and that the absence of the SCF(Skp2) complex in the nucleus of SK-UT-1B cells is the mechanism underlying the ubiquitination defect observed in this cell line. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271634 |
|
|
Homo sapiens |
HCT-116 Cell |
| pmid |
sentence |
| 17205132 |
FBXW8 associates with CUL1 or CUL7 and forms a complex with SKP1 and RBX1. We next investigated whether in vitro ubiquitination of cyclin D1 through the SCF-like (SCFL) complex FBXW8 (SKP1-CUL7-FBXW8-RBX1/SCFLFBXW8) requires phosphorylation of cyclin D1 at Thr286 (Fig. 3F). Polyubiquitination through SCFLFBXW8 was dramatically reduced by the depletion of ERK2 (lane 2). Furthermore, cyclin D1 polyubiquitination was largely prevented by the alanine-for-Thr286 substitution (T286A, lane 3), suggesting that phosphorylation of cyclin D1 at Thr286 is necessary for ubiquitination by SCFLFBXW8. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
LRRC4 | down-regulates quantity by repression
transcriptional regulation
|
CCND1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-264056 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25526788 |
LRRC4/NGL-2 can delay the cell cycle in late G1 by increasing the expression of cell cycle inhibitory molecules (p21, p27) and reducing the expression of cell cycle regulatory proteins (CyclinD1, CDK2, CyclinE, CDK4) via the inhibition of K-Ras/c-Raf/ERK/MAPK, PI-3K/AKT/NF- κB, p70S6/PKC and STAT3, and the upregulation of the JNK2/c-Jun/mp53 signaling pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
RBPJ/NOTCH | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.597 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-209753 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11486031 |
Using this inducible system, we show that Notchic activates transcription of the cyclin D1 gene with rapid kinetics. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
GLI1 | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.563 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-188869 |
|
|
Homo sapiens |
Breast Cancer Cell, Lung Cancer Cell |
| pmid |
sentence |
| 19860666 |
GLI activators bind to GACCACCCA motif to regulate transcription of GLI1, PTCH1, PTCH2, HHIP1, MYCN, CCND1, CCND2, BCL2, CFLAR, FOXF1, FOXL1, PRDM1 (BLIMP1), JAG2, GREM1, and Follistatin |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-199126 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23074268 |
Canonical hh signaling plays an essential role in cell proliferation throught introduction of the genes encoding cyclin d1 and n-myc |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
AP1 | up-regulates
transcriptional regulation
|
CCND1 |
0.606 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253215 |
|
|
Homo sapiens |
Lung Cancer Cell Line |
| pmid |
sentence |
| 12509763 |
Substrates for ERK1/2 include nuclear proteins such as C-JUN, this leads to activation of the AP-1 transcription factor, which is made up of FOS-JUN heterodimers.|As a result of stimulating these transcriptional regulators, key cell-cycle regulatory proteins, such as D-type cyclins, are expressed, which enables the cell to progress through the G1 phase of the cell-cycle. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia |
| + |
CCND1 | up-regulates quantity by expression
transcriptional regulation
|
MSI1 |
0.288 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-165186 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20443831 |
We hypothesized that cyclin d1 may induce notch1 activity either by repressing numb or by inducing musashi 1 expression |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
UHRF2 | down-regulates quantity by destabilization
ubiquitination
|
CCND1 |
0.298 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271885 |
|
|
Chlorocebus aethiops |
COS-7 Cell |
| pmid |
sentence |
| 21952639 |
We found that NIRF directly ubiquitinated cyclins D1 and E1, as evidenced by the appearance of the tail (Fig. 4B). In summary, the above findings suggest that NIRF tightly cooperates with the core cell cycle machinery and induces G1 arrest, which is accompanied by ubiquitination of cyclins D1 and E1. |
|
| Publications: |
1 |
Organism: |
Chlorocebus Aethiops |
| + |
CCND1 | up-regulates
|
NOTCH1 |
0.624 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-165189 |
|
|
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 20443831 |
The mechanism by which cyclin d1 enhances notch1 activity in different cell types remains to be determined;the current studies demonstrate for the first time that notch1 activity is induced by cyclin d1. The expression of cyclin d1 sirna reduced notch1 activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Breast |
| Pathways: | Acute Myeloid Leukemia |
| + |
SNAI2 | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.472 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255176 |
|
|
Homo sapiens |
Breast Cancer Cell Line |
| pmid |
sentence |
| 21044962 |
knockdown of SLUG in SLUG-high breast cancer cells elevated the levels of UbcH5c while decreasing the level of cyclin D1 protein. SLUG is recruited at the E2-box sequence at the UbcH5c gene promoter along with the corepressor CtBP1 and the effector HDAC1 to silence the expression of this gene. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NOTCH | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254349 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11486031 |
Moreover, as determined by using coimmunoprecipitation assays, each maml protein was found to be capable of forming a multiprotein complex with the intracellular domain of each notch receptor (icn1 to -4) and csl in vivo |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia |
| + |
STAT3 | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.78 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255411 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 18177723 |
We identified cyclin D1 as a STAT3 target gene product downregulated in satellite cells from IL-6-deficient muscle in vitro and in vivo. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253049 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16510571 |
Mutagenesis of STAT3 binding sites within the cyclin D1 promoter and chromatin immunoprecipitation studies showed an association between STAT3 and the transcriptional regulation of the human cyclin D1 gene. |
|
| Publications: |
2 |
Organism: |
Mus Musculus, Homo Sapiens |
| Tissue: |
Skeletal Muscle |
| Pathways: | Acute Myeloid Leukemia |
| + |
LEF1 | up-regulates quantity by expression
transcriptional regulation
|
CCND1 |
0.585 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256281 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19653274 |
Expression of Lef-1 FL, but not the newly identified Lef-1 Deltaexon VI, induced the expression of the cell cycle regulating proteins c-myc and cyclin D1 in cooperation with beta-catenin and it enhanced cell proliferation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CCND1 | down-regulates
|
Skeletal_muscle_differentiation |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255351 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20219869 |
Importantly, NF-kB can promote the expression and stability of cyclin D1 in muscle (4, 35, 39, 132), leading to increased cell proliferation and inhibition of differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Skeletal Muscle |
| + |
Cullin 7-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
CCND1 |
0.46 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271633 |
|
|
Homo sapiens |
HCT-116 Cell |
| pmid |
sentence |
| 17205132 |
FBXW8 associates with CUL1 or CUL7 and forms a complex with SKP1 and RBX1. We next investigated whether in vitro ubiquitination of cyclin D1 through the SCF-like (SCFL) complex FBXW8 (SKP1-CUL7-FBXW8-RBX1/SCFLFBXW8) requires phosphorylation of cyclin D1 at Thr286 (Fig. 3F). Polyubiquitination through SCFLFBXW8 was dramatically reduced by the depletion of ERK2 (lane 2). Furthermore, cyclin D1 polyubiquitination was largely prevented by the alanine-for-Thr286 substitution (T286A, lane 3), suggesting that phosphorylation of cyclin D1 at Thr286 is necessary for ubiquitination by SCFLFBXW8. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RASSF1 | down-regulates quantity by repression
post transcriptional regulation
|
CCND1 |
0.56 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259455 |
|
|
Homo sapiens |
NCI-H1299 Cell |
| pmid |
sentence |
| 12024041 |
RASSF1A expression dramatically inhibits native cyclin D1 accumulation | Regulation of cyclin D1 accumulation by RASSF1A is independent of the cyclin D1 promoter and likely occurs through inhibition of mRNA translation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CYLD | up-regulates
|
CCND1 |
0.401 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-146777 |
|
|
Homo sapiens |
Skin Cancer Cell |
| pmid |
sentence |
| 16713561 |
Cyld was also recently shown to deubiquitylate the p50 and p52 co-activator bcl-3, leading to both cyclin d1 expression and proliferation in keratinocytes |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NfKb-p65/p50 | up-regulates quantity by expression
|
CCND1 |
0.483 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255358 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20219869 |
Importantly, NF-kB can promote the expression and stability of cyclin D1 in muscle (4, 35, 39, 132), leading to increased cell proliferation and inhibition of differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Skeletal Muscle |
| Pathways: | Acute Myeloid Leukemia |
| + |
MECP2 | down-regulates quantity by repression
transcriptional regulation
|
CCND1 |
0.276 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254571 |
|
|
Homo sapiens |
MCF-7 Cell |
| pmid |
sentence |
| 15870696 |
Valproate (VPA) induces silencing of the ERalpha, cyclin D1 and pS2 promoters. Chromatin immunoprecipitation (ChIP) analysis demonstrates that VPA induces recruitment of the 5-MeCpG binding protein MeCP2 to the ERalpha A promoter and also to the pS2 and cyclin D1 promoters |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia |
| + |
FBXO31 | down-regulates quantity by destabilization
binding
|
CCND1 |
0.423 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277379 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 29343641 |
FBXO31 serves as the substrate-recognition component of the SKP/Cullin/F-box protein class of E3 ubiquitin ligases and has been shown to direct degradation of pivotal cell-cycle regulatory proteins including cyclin D1 and the p53 antagonist MDM2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
CCND1
- 
- 