Molecular basis of Pirh2-mediated p53 ubiquitylation
2008 (English)In: NATURE STRUCTURAL and MOLECULAR BIOLOGY, ISSN 1545-9985 , Vol. 15, no 12, 1334-1342 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2008. Vol. 15, no 12, 1334-1342 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-16184DOI: 10.1038/nsmb.1521OAI: oai:DiVA.org:liu-16184DiVA: diva2:133371