+ |
PML-RARalpha | up-regulates activity
|
CCNA1 |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-256373 |
|
|
Homo sapiens |
|
pmid |
sentence |
11090075 |
We show that the ectopic expression of PML-RARα is sufficient to elevate levels of cyclin A1 in U937 myeloid leukemia cells and cyclin A1 is negatively regulated by the RARα pathway. |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
Pathways: | Acute Myeloid Leukemia, FLT3 in AML, Onco-fusion proteins in AML |
+ |
PML-RARalpha | up-regulates activity
|
JUN |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-259940 |
|
|
Homo sapiens |
MCF-7 Cell |
pmid |
sentence |
8415704 |
PML-RAR alpha chimera cooperates with c-Jun and, strikingly, with c-Fos to stimulate the transcription of both synthetic and natural reporter genes containing an AP-1 site |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
Pathways: | Acute Myeloid Leukemia |
+ |
PML-RARalpha | up-regulates quantity by expression
transcriptional regulation
|
ID1 |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-255728 |
|
|
Homo sapiens |
|
pmid |
sentence |
18025157 |
We show that the ID1 and ID2 promoters are activated by PML-RARα but, unexpectedly, not by wild-type RARα/RXR. In contrast, PML-RARα transactivated the promoter more than 12-fold in an ATRA-dependent fashion. |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
Pathways: | Acute Myeloid Leukemia, FLT3 in AML |
+ |
PML-RARalpha | up-regulates activity
binding
|
GATA2 |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-259941 |
|
|
Mus musculus |
BA/F3 Cell |
pmid |
sentence |
10938104 |
We provide evidence that GATA-2 can physically associate with PML-RARα. Functional experiments further demonstrated that this interaction has the capacity to render GATA-dependent transcription inducible by retinoic acid, raising the possibility that GATA target genes may be involved in the molecular pathogenesis of APL. |
|
Publications: |
1 |
Organism: |
Mus Musculus |
+ |
PML-RARalpha | down-regulates
|
Differentiation |
0.7 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-255724 |
|
|
Homo sapiens |
|
pmid |
sentence |
20966922 |
APL cells closely resemble normal promyelocytes, a specific stage of the granulocytic differentiation pathway, suggesting that PML–RARα blocks the normal myeloid differentiation programme. |
|
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-255723 |
|
|
Homo sapiens |
U-937 Cell |
pmid |
sentence |
8394219 |
We expressed the PML-RARa protein in U937 myeloid precursor cells and showed that they lost the capacity to differentiate under the action of different stimuli (vitamin Ds and transforming growth factor pl), acquired enhanced sensitivity to retinoic acid, and exhibited a higher growth rate consequent to diminished apoptotic cell death. |
|
Publications: |
2 |
Organism: |
Homo Sapiens |
Pathways: | Acute Myeloid Leukemia, FLT3 in AML, Onco-fusion proteins in AML |
+ |
PML-RARalpha | down-regulates quantity by repression
transcriptional regulation
|
CEBPA |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-255726 |
|
|
Homo sapiens |
|
pmid |
sentence |
19797526 |
We therefore conclude that PML-RARα–mediated repression of C/EBPα is driven through a DNA methylation pathway. In accordance with this finding, a recent study in human APL samples described increased C/EBPα promoter methylation, consistent with the ability of PML-RARα to recruit corepressor complexes. Moreover, the PML-RARα effect on C/EBPα repression does not seem to be mediated via direct binding. |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
Pathways: | Acute Myeloid Leukemia, FLT3 in AML, Onco-fusion proteins in AML |
+ |
RXRA | up-regulates activity
binding
|
PML-RARalpha |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-255804 |
|
|
Mus musculus |
|
pmid |
sentence |
17613434 |
RXR Binding Increases the DNA-Binding Affinity of PML/RARA. Here, we demonstrate that the presence of the RARA heterodimeric partner RXR in the PML/RARA complex is required for leukemogenesis in transgenic mice. RXR greatly facilitates the binding of PML/RARA to DNA, but titration of RXR by PML/RARA could also contribute to transformation. |
|
Publications: |
1 |
Organism: |
Mus Musculus |
Pathways: | Acute Myeloid Leukemia |
+ |
diarsenic trioxide | down-regulates quantity by destabilization
chemical inhibition
|
PML-RARalpha |
0.8 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-259924 |
|
|
Homo sapiens |
|
pmid |
sentence |
24344243 |
ATO was shown to degrade PML-RARa via its PML moiety further reinforcing the idea that APL is addicted to the PML-RARa oncoprotein |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
Pathways: | Acute Myeloid Leukemia, FLT3 in AML |
+ |
PML-RARalpha | up-regulates activity
binding
|
SP1 |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-255749 |
|
|
Homo sapiens |
U-937 Cell |
pmid |
sentence |
18025157 |
We show that the ID1 and ID2 promoters are activated by PML-RARalpha but, unexpectedly, not by wild-type RARalpha/RXR. Our data support a model in which the PML-RARalpha fusion protein regulates a novel class of target genes by interaction with the Sp1 and NF-Y transcription factors, without directly binding to the DNA, defining a gain-of-function for the oncoprotein. |
|
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-255729 |
|
|
in vitro |
|
pmid |
sentence |
18025157 |
We show that PML-RARα physically interacts with Sp1 in the absence of DNA. In this report, we show that PML-RARα interacts with Sp1 and may interfere with the expression of genes that are not normally regulated by retinoic acid receptors. |
|
Publications: |
2 |
Organism: |
Homo Sapiens, In Vitro |
Pathways: | Acute Myeloid Leukemia, FLT3 in AML |
+ |
PML-RARalpha | up-regulates quantity by expression
transcriptional regulation
|
CCNA1 |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-255725 |
|
|
Homo sapiens |
|
pmid |
sentence |
11090075 |
Overexpression of cyclin A1 observed in APL cells is caused by the expression of the aberrant fusion proteins, PML-RARα and PLZF-RARα. PML-RARα itself can lead to activation of the cyclin A1 promoter.Since both fusion proteins disrupt the normal RARα function, our results strongly suggested that the RARα pathway negatively regulates the expression of cyclin A1 and that this negative regulation is disrupted by the aberrant fusion proteins. |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
Pathways: | Acute Myeloid Leukemia, FLT3 in AML, Onco-fusion proteins in AML |
+ |
PML-RARalpha | up-regulates activity
|
AP1 |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-261507 |
|
|
Homo sapiens |
MCF-7 Cell |
pmid |
sentence |
8415704 |
PML-RAR alpha chimera cooperates with c-Jun and, strikingly, with c-Fos to stimulate the transcription of both synthetic and natural reporter genes containing an AP-1 site |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
Pathways: | Acute Myeloid Leukemia, FLT3 in AML, Onco-fusion proteins in AML |
+ |
PML-RARalpha | up-regulates quantity
transcriptional regulation
|
MYB |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-259939 |
|
|
Homo sapiens |
Promyelocyte |
pmid |
sentence |
30335887 |
PML/RARa blocks the differentiation and promotes the proliferation of acute promyelocytic leukemia through activating MYB expression by transcriptional and epigenetic regulation mechanisms. |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
+ |
PML-RARalpha | up-regulates activity
|
MYC |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-256374 |
|
|
Homo sapiens |
|
pmid |
sentence |
19855079 |
We demonstrate that in addition to blocking myeloid differentiation, PLZF-RARα also promotes proliferation/self-renewal via the aberrant regulation of cell cycle–associated genes such as c-Myc, providing a basis for studying the aberrant response of this leukemia subtype to retinoic acid. |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
Pathways: | Acute Myeloid Leukemia, FLT3 in AML |
+ |
all-trans-retinoic acid | down-regulates quantity by destabilization
chemical inhibition
|
PML-RARalpha |
0.8 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-259926 |
|
|
Homo sapiens |
|
pmid |
sentence |
19029980 |
Retinoic acid and arsenic synergize to clear LICs through cooperative PML-RARA degradation, this combination does not enhance differentiation. |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
Pathways: | Acute Myeloid Leukemia, FLT3 in AML |
+ |
PML-RARalpha | up-regulates quantity by expression
transcriptional regulation
|
ID2 |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-255727 |
|
|
Homo sapiens |
|
pmid |
sentence |
18025157 |
Also comparable with ID1, RARα, RXR, PML, PLZF-RARα, and RARα/RXR did not transactivate the ID2 promoter, whereas PML-RARα did. Together, these data show that like ID1, ID2 may also be transactivated by PML-RARα without direct DNA binding of the fusion protein. |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
+ |
PML-RARalpha | up-regulates
|
Proliferation |
0.7 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-255722 |
|
|
Homo sapiens |
U-937 Cell |
pmid |
sentence |
8394219 |
We expressed the PML-RARa protein in U937 myeloid precursor cells and showed that they lost the capacity to differentiate under the action of different stimuli (vitamin Ds and transforming growth factor pl), acquired enhanced sensitivity to retinoic acid, and exhibited a higher growth rate consequent to diminished apoptotic cell death. |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
Pathways: | Acute Myeloid Leukemia, FLT3 in AML, Onco-fusion proteins in AML |
+ |
PML-RARalpha | up-regulates activity
binding
|
NFY |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-255747 |
|
|
Homo sapiens |
HEP-3B Cell |
pmid |
sentence |
18025157 |
We show that the ID1 and ID2 promoters are activated by PML-RARalpha but, unexpectedly, not by wild-type RARalpha/RXR. Our data support a model in which the PML-RARalpha fusion protein regulates a novel class of target genes by interaction with the Sp1 and NF-Y transcription factors, without directly binding to the DNA, defining a gain-of-function for the oncoprotein. |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
Pathways: | Acute Myeloid Leukemia, FLT3 in AML |