ARF regulates the stability of p16 protein Via REGγ-dependent proteasome degradation Journal Article


Authors: Kobayashi, T.; Wang, J.; Al-Ahmadie, H.; Abate-Shen, C.
Article Title: ARF regulates the stability of p16 protein Via REGγ-dependent proteasome degradation
Abstract: The cell-cycle regulatory gene INK4A-ARF (CDKN2A) has two alternative transcripts that produce entirely different proteins, namely p14ARF and p16, which have complementary functions as regulators of p53 and pRB tumor suppressor pathways, respectively. The unusual organization of INK4A-ARF has long led to speculation of a need for coordinated regulation of p14 ARF and p16. We now show that p14ARF (ARF) regulates the stability of p16 protein in human cancer cell lines, as well as in mouse embryonic fibroblasts (MEFs). In particular, ARF promotes rapid degradation of p16 protein, which is mediated by the proteasome and, more specifically, by interaction of ARF with one of its subunits, REGγ. Furthermore, this ARF-dependent destabilization of p16 can be abrogated by knockdown of REGγ or by pharmacologic blockade of its nuclear export. Thus, our findings have uncovered a novel crosstalk of 2 key tumor suppressors mediated by aREGγ-dependent mechanism. The ability of ARF to control p16 stability may influence cell-cycle function. Implications: The ability of ARF to control p16 stability may influence cell cycle function. © 2013 AACR.
Keywords: controlled study; unclassified drug; human cell; cell cycle; protein p16; proteasome; protein degradation; protein stability; genetic transcription; protein interaction; protein p53; tumor suppressor gene; regulatory mechanism; human cell culture; membrane protein; arf protein; cyclin dependent kinase inhibitor 2a; cell cycle regulation; protein p14; reg gamma protein; nuclear export signal
Journal Title: Molecular Cancer Research
Volume: 11
Issue: 8
ISSN: 1541-7786
Publisher: American Association for Cancer Research  
Date Published: 2013-08-01
Start Page: 828
End Page: 833
Language: English
DOI: 10.1158/1541-7786.mcr-13-0207
PROVIDER: scopus
PMCID: PMC3748223
PUBMED: 23817020
DOI/URL:
Notes: --- - "Export Date: 1 October 2013" - "CODEN: MCROC" - "Source: Scopus"
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors