Summary

Name CDKN2A
Full Name Tumor suppressor ARF
Synonyms Alternative reading frame, ARF, Cyclin-dependent kinase inhibitor 2A, p14ARF | CDKN2, MLM
Primary ID Q8N726
Links - -
Type protein
Relations 16
Pathways Acute Myeloid Leukemia, AML1-ETO in AML, DNMT3A in AML, Onco-fusion proteins in AML, NPM1 in AML, AML_TRIPLETS, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Triple mutant AML, NPM1_new
Function Capable of inducing cell cycle arrest in G1 and G2 phases. Acts as a tumor suppressor. Binds to MDM2 and blocks its nucleocytoplasmic shuttling by sequestering it in the nucleolus. This inhibits the oncogenic action of MDM2 by blocking MDM2-induced degradation of p53 and enhancing p53-dependent transactivation and apoptosis. Also induces G2 arrest and apoptosis in a p53-independent manner by preventing the activation of cyclin B1/CDC2 complexes. Binds to BCL6 and down-regulates BCL6-induced transcriptional repression. Binds to E2F1 and MYC and blocks their transcriptional activator activity but has no effect on MYC transcriptional repression. Binds to TOP1/TOPOI and stimulates its activity. This complex binds to rRNA gene promoters and may play a role in rRNA transcription and/or maturation. Interacts with NPM1/B23 and promotes its polyubiquitination and degradation, thus inhibiting rRNA processing. Interacts with COMMD1 and promotes its 'Lys63'-linked polyubiquitination. Interacts with UBE2I/UBC9 and enhances sumoylation of a number of its binding partners including MDM2 and E2F1. Binds to HUWE1 and represses its ubiquitin ligase activity. May play a role in controlling cell proliferation and apoptosis during mammary gland development. Isoform smARF may be involved in regulation of autophagy and caspase-independent cell death; the short-lived mitochondrial isoform is stabilized by C1QBP.

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Relations

Regulator Mechanism target score
+ up-regulates activity img/direct-activation.png phosphorylation ATR 0.402
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition
+ down-regulates quantity by repression img/direct_inhibition.png transcriptional regulation CDKN2A 0.308
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation CDKN2A 0.269
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, Onco-fusion proteins in AML, NPM1_new
+ up-regulates activity img/direct-activation.png binding CDKN2A 0.575
Publications: 1 Organism: Mus Musculus
Pathways:Acute Myeloid Leukemia, DNMT3A in AML, Onco-fusion proteins in AML, NPM1 in AML, AML_TRIPLETS, Triple mutant AML, NPM1_new
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation CDKN2A 0.378
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation CDKN2A 0.476
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/direct_inhibition.png transcriptional regulation CDKN2A 0.411
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png CDKN2A 0.7
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition
+ down-regulates quantity by repression img/direct_inhibition.png transcriptional regulation CDKN2A 0.348
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png binding NPM1 0.575
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, DNMT3A in AML, Onco-fusion proteins in AML, NPM1 in AML, AML_TRIPLETS, Triple mutant AML, NPM1_new
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination CDKN2A 0.379
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/direct_inhibition.png transcriptional regulation CDKN2A 0.5
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination CDKN2A 0.607
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/indirect-activation.png TP53 0.782
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, AML1-ETO in AML, DNMT3A in AML, Onco-fusion proteins in AML, NPM1 in AML, AML_TRIPLETS, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Malignant Melanoma, Triple mutant AML, NPM1_new
+ down-regulates activity img/direct_inhibition.png relocalization MDM2 0.757
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, AML1-ETO in AML, DNMT3A in AML, NPM1 in AML, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Malignant Melanoma, Triple mutant AML, NPM1_new
+ down-regulates img/direct_inhibition.png transcriptional regulation CDKN2A 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, AML1-ETO in AML, Onco-fusion proteins in AML