| + |
GSK3B | down-regulates 
phosphorylation
|
MCL1 |
0.515 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-145200 |
Ser159 |
NNTSTDGsLPSTPPP |
Homo sapiens |
|
| pmid |
sentence |
| 16543145 |
We investigated the role of glycogen synthase kinase-3 (gsk-3), which is inactivated by akt, for its role in the regulation of apoptosis. Upon il-3 withdrawal, protein levels of mcl-1 decreased but were sustained by pharmacological gsk-3, which prevented cytochrome c release and apoptosis. Mcl-1 was phosphorylated by gsk-3 at a conserved gsk-3 phosphorylation site (s159). S159 phosphorylation of mcl-1 was induced by il-3 withdrawal or pi3k inhibition and prevented by akt or gsk-3, and it led to increased ubiquitinylation and degradation of mcl-1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia |
| + |
GSK3B | down-regulates quantity by destabilization
phosphorylation
|
MCL1 |
0.515 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251242 |
Ser159 |
NNTSTDGsLPSTPPP |
Mus musculus |
FL5.12 Cell |
| pmid |
sentence |
| 16543145 |
MCL-1 was phosphorylated by GSK-3 at a conserved GSK-3 phosphorylation site (S159). S159 phosphorylation of MCL-1 was induced by IL-3 withdrawal or PI3K inhibition and prevented by AKT or inhibition of GSK-3, and it led to increased ubiquitinylation and degradation of MCL-1. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia |
| + |
GSK3A | down-regulates quantity by destabilization
phosphorylation
|
MCL1 |
0.469 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251217 |
Ser159 |
NNTSTDGsLPSTPPP |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 16543145 |
MCL-1 was phosphorylated by GSK-3 at a conserved GSK-3 phosphorylation site (S159). Glycogen Synthase Kinase-3 Regulates Mitochondrial Outer Membrane Permeabilization and Apoptosis by Destabilization of MCL-1. threonine 163, which represents the GSK-3 priming phosphorylation in this protein |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK1 | up-regulates 
phosphorylation
|
MCL1 |
0.543 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-179808 |
Thr163 |
TDGSLPStPPPAEEE |
Homo sapiens |
|
| pmid |
sentence |
| 18676833 |
We found that jnk phosphorylated ser-121 and thr-163 of mcl-1 in response to stimulation with h(2)o(2) and that transfection of unphosphorylatable mcl-1 resulted in an enhanced anti-apoptotic activity in response to stimulation with h(2)o(2). Jnk-dependent phosphorylation and thus inactivation of mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-92593 |
Thr163 |
TDGSLPStPPPAEEE |
Homo sapiens |
|
| pmid |
sentence |
| 12223490 |
We found that jnk phosphorylated ser-121 and thr-163 of mcl-1 in response to stimulation with h(2)o(2) and that transfection of unphosphorylatable mcl-1 resulted in an enhanced anti-apoptotic activity in response to stimulation with h(2)o(2). Jnk-dependent phosphorylation and thus inactivation of mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
MAPK8 | up-regulates
phosphorylation
|
MCL1 |
0.543 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-179816 |
Thr163 |
TDGSLPStPPPAEEE |
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 18676833 |
Mcl-1 can be rapidly degraded by certain death-inducing signals, but it is able to be readily induced by diverse survival cytokines such as epidermal growth factor, vascular endothelial growth factor, granulocyt-macrophage colony-stimulating factor, and interleukin 3 through phosphatidy-linositol-3-oh kinase/akt, mek/mapk, or janus-activated kinase/stat signaling cascades |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-92597 |
Thr163 |
TDGSLPStPPPAEEE |
Homo sapiens |
|
| pmid |
sentence |
| 12223490 |
We found that jnk phosphorylated ser-121 and thr-163 of mcl-1 in response to stimulation with h(2)o(2) and that transfection of unphosphorylatable mcl-1 resulted in an enhanced anti-apoptotic activity in response to stimulation with h(2)o(2). Jnk-dependent phosphorylation and thus inactivation of mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, COVID-19 Causal Network |
| + |
MAPK3 | up-regulates
phosphorylation
|
MCL1 |
0.45 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-179812 |
Thr163 |
TDGSLPStPPPAEEE |
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 18676833 |
We then showed that erk could phosphorylate mcl-1 at two consensus residues, thr 92 and 163, which is required for the association of mcl-1 and pin1, resulting in stabilization of mcl-1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CyclinB/CDK1 | down-regulates quantity by destabilization
phosphorylation
|
MCL1 |
0.431 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-216900 |
Thr92 |
EVPDVTAtPARLLFF |
Homo sapiens |
|
| pmid |
sentence |
| 18676833 |
Mcl-1 is phosphorylated at two sites in mitosis, ser64 and thr92. Phosphorylation of thr92 by cyclin-dependent kinase 1 (cdk1)-cyclin b1 initiates degradation of mcl-1 in cells arrested in mitosis by microtubule poisons. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDK1 | down-regulates quantity by destabilization
phosphorylation
|
MCL1 |
0.475 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-165867 |
Thr92 |
EVPDVTAtPARLLFF |
Homo sapiens |
|
| pmid |
sentence |
| 20526282 |
Mcl-1 is phosphorylated at two sites in mitosis, ser64 and thr92. Phosphorylation of thr92 by cyclin-dependent kinase 1 (cdk1)-cyclin b1 initiates degradation of mcl-1 in cells arrested in mitosis by microtubule poisons. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia |
| + |
BBC3 | down-regulates
binding
|
MCL1 |
0.742 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-133817 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15694340 |
Only bimbh3 and bbc3 had comparable strong affinities for all the prosurvival proteins. The members that promote cell survival, including mammalian bcl-2, bcl-xl,bcl-w, mcl-1, and a1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MCL1 | down-regulates
binding
|
BAX |
0.724 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-151787 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17289999 |
Which of the multiple pro-survival proteins that can bind Bax (fig. S15A) can functionally restrain it? Mcl-1 must, because neutralizing Mcl-1 by enforced Noxa expression rendered MEFs containing only Bax (Bak KO cells) sensitive to the Bad BH3 mimetic ABT-737 (Fig. 4A), which inactivates Bcl-2, Bcl-xL, and Bcl-w |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, MLL fusion protein in AML, COVID-19 Causal Network, SARS-COV APOPTOSIS |
| + |
PSMB8 | down-regulates quantity by destabilization
|
MCL1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261974 |
|
|
Homo sapiens |
Carotid Atherosclerotic Plaque |
| pmid |
sentence |
| 19443843 |
Surprisingly, siRNA knockdown of PSMB8 (LMP7), an ‘immunoproteasome’ component, reversed IFNγ-induced sensitivity to Fas ligation and prevented Fas/IFNγ-induced degradation of Mcl-1, but did not protect p-Bcl-2 or p-Bcl-XL. Proteasome inhibition markedly increased Mcl-1, p-Bcl-2, and p-Bcl-XL levels after IFNγ treatment |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DOT1L | up-regulates quantity by expression 
transcriptional regulation
|
MCL1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255881 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 27856324 |
Previously, we found that MLL-AF4 binds to the BCL-2 gene and directly activates it through DOT1L recruitment and increased H3K79me2/3 levels. MLL-AF4 directly controls the active transcription of both BCL-2 and MCL-1 […]. Of all the BCL-2 family members, only BCL-2 and MCL-1 are directly activated by MLL-AF4. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, MLL fusion protein in AML |
| + |
LGALS3 | up-regulates quantity by stabilization
|
MCL1 |
0.257 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261905 |
|
|
Homo sapiens |
K-562 Cell |
| pmid |
sentence |
| 21821001 |
Our study also showed that a number of K562 cells survived despite the apoptotic stimuli. Within these surviving cells, galectin-3 was upregulated through newly synthesized protein. Notably, inducible galectin-3, which stabilized the pro-survival Bcl-2 family proteins Mcl-1, Bcl-xL, and Bcl-2, was essential for anti-apoptosis. Unpredictably, GSK-3β was critical for inducible galectin-3 expression as well as for cell survival. As summarized in Fig. 4C, we not only found inducible galectin-3 has an anti-apoptotic effect, but we also identified a GSK-3β-regulated mechanism for apoptotic resistance in K562 cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
HUWE1 | down-regulates quantity by destabilization
ubiquitination
|
MCL1 |
0.517 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261909 |
|
|
Homo sapiens |
MCF-7 Cell |
| pmid |
sentence |
| 28939105 |
Mule was identified as Mcl-1 ubiquitin ligase E3 to promote Mcl-1 degradation via the proteasomal pathway [46]. We found that knockdown of Mule (Fig. 4C) but not β-TRCP or FBXW7 (data not shown) prevented Mcl-1 downregulation caused by PKCη depletion. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ERK1/2 | up-regulates
phosphorylation
|
MCL1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270158 |
|
|
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 18676833 |
We then showed that erk could phosphorylate mcl-1 at two consensus residues, thr 92 and 163, which is required for the association of mcl-1 and pin1, resulting in stabilization of mcl-1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, COVID-19 Causal Network |
| + |
PRKCH | up-regulates quantity by stabilization
|
MCL1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261908 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28939105 |
The results of our present study show that PKCη positively regulates the anti-apoptotic Bcl-2 family protein Mcl-1 by preventing its degradation via the proteasomal pathway involving Mcl-1 ubiquitin ligase Mule. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Gbeta | up-regulates
phosphorylation
|
MCL1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270042 |
|
|
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 18676833 |
We then showed that erk could phosphorylate mcl-1 at two consensus residues, thr 92 and 163, which is required for the association of mcl-1 and pin1, resulting in stabilization of mcl-1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
N-[4-(2-tert-butylphenyl)sulfonylphenyl]-2,3,4-trihydroxy-5-[(2-propan-2-ylphenyl)methyl]benzamide | down-regulates
chemical inhibition
|
MCL1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-207465 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NPTX1 | down-regulates quantity 
|
MCL1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260413 |
|
|
Homo sapiens |
MHCC-97 Cell, SMMC-7721 Cell |
| pmid |
sentence |
| 31113871 |
We found that the protein levels of BCL2-associated agonist of cell death (BAD) and BCL2-associated X protein (BAX) were increased in NPTX1-overexpressing SMMC-7721 and MHCC-97h cells relative to control cells. In contrast, decreased levels of myeloid cell leukemia sequence 1 (Mcl-1) and B-cell lymphoma-2 (Bcl-2) were found in NPTX1-overexpressing SMMC-7721 and MHCC-97h cells relative to control |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRIM17 | down-regulates quantity by destabilization
polyubiquitination
|
MCL1 |
0.456 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272032 |
|
|
Mus musculus |
Neuro-2a Cell |
| pmid |
sentence |
| 22976837 |
Here, we identified Trim17 as a novel E3 ubiquitin-ligase for Mcl-1. Indeed, Trim17 co-immunoprecipitated with Mcl-1. Trim17 ubiquitinated Mcl-1 in vitro. Overexpression of Trim17 decreased the protein level of Mcl-1 in a phosphorylation- and proteasome-dependent manner. Finally, knock down of Trim17 expression reduced both ubiquitination and degradation of Mcl-1 in neurons. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
Obatoclax mesylate | down-regulates activity
chemical inhibition
|
MCL1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262025 |
|
|
in vitro |
|
| pmid |
sentence |
| 23515850 |
Obatoclax and its predecessor analogs bind to BCL-2, BCL-XL, BCL-w, BCL-B, BFL-1, and MCL-1 in vitro|The ability of obatoclax to inhibit MCL-1 may be particularly important, given that several hematological malignancies appear to depend on this protein for survival, such as acute lymphoblastic leukemia (ALL),44 CLL,44 multiple myeloma,45 and diffuse large B-cell lymphoma (DLBCL) |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
MCL1 | down-regulates
binding
|
BAK1 |
0.608 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-149774 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17289999 |
Bax is held in check by mcl1, bcl-2, and either bcl2l1 or bcl2l2, or by all four. They bind a primed conformer of bak or bax |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, MLL fusion protein in AML |
3.0
MCL1
- 
- 