Format

Send to

Choose Destination
Nat Struct Mol Biol. 2008 Dec;15(12):1334-42. doi: 10.1038/nsmb.1521. Epub 2008 Nov 30.

Molecular basis of Pirh2-mediated p53 ubiquitylation.

Author information

1
Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Ontario M5G1L7, Canada.

Abstract

Pirh2 (p53-induced RING-H2 domain protein; also known as Rchy1) is an E3 ubiquitin ligase involved in a negative-feedback loop with p53. Using NMR spectroscopy, we show that Pirh2 is a unique cysteine-rich protein comprising three modular domains. The protein binds nine zinc ions using a variety of zinc coordination schemes, including a RING domain and a left-handed beta-spiral in which three zinc ions align three consecutive small beta-sheets in an interleaved fashion. We show that Pirh2-p53 interaction is dependent on the C-terminal zinc binding module of Pirh2, which binds to the tetramerization domain of p53. As a result, Pirh2 preferentially ubiquitylates the tetrameric form of p53 in vitro and in vivo, suggesting that Pirh2 regulates protein turnover of the transcriptionally active form of p53.

PMID:
19043414
PMCID:
PMC4075976
DOI:
10.1038/nsmb.1521
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center