Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Cycle. 2013 Sep 1;12(17):2733-7. doi: 10.4161/cc.25785. Epub 2013 Aug 5.

Pirh2: an E3 ligase with central roles in the regulation of cell cycle, DNA damage response, and differentiation.

Author information

1
Ontario Cancer Institute; University Health Network and Department of Medical Biophysics; University of Toronto; Toronto, Ontario, Canada.

Abstract

Ubiquitylation is currently recognized as a major posttranslational modification that regulates diverse cellular processes. Pirh2 is a ubiquitin E3 ligase that regulates the turnover and functionality of several proteins involved in cell proliferation and differentiation, cell cycle checkpoints, and cell death. Here we review the role of Pirh2 as a regulator of the DNA damage response through the ubiquitylation of p53, Chk2, p73, and PolH. By ubiquitylating these proteins, Pirh2 regulates cell cycle checkpoints and cell death in response to DNA double-strand breaks or the formation of bulky DNA lesions. We also discuss how Pirh2 affects cell proliferation and differentiation in unstressed conditions through ubiquitylation and degradation of c-Myc, p63, and p27(kip1). Finally, we link these different functions of Pirh2 to its role as a tumor suppressor in mice and as a prognosis marker in various human cancer subtypes.

KEYWORDS:

Chk2; Pirh2; c-Myc; p27Kip1; p53; p63; p73; polH; ubiquitylation

PMID:
23966173
PMCID:
PMC3899186
DOI:
10.4161/cc.25785
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Taylor & Francis Icon for PubMed Central
    Loading ...
    Support Center