The ubiquitin ligase COP1 is a critical negative regulator of p53

David Dornan, Ingrid Wertz, Harumi Shimizu, David Arnott, Gretchen D. Frantz, Patrick Dowd, Karen O' Rourke, Hartmut Koeppen and Vishva M. Dixit ()
Additional contact information
David Dornan: Genentech, Inc.
Ingrid Wertz: Genentech, Inc.
Harumi Shimizu: Genentech, Inc.
David Arnott: Genentech, Inc.
Gretchen D. Frantz: Genentech, Inc.
Patrick Dowd: Genentech, Inc.
Karen O' Rourke: Genentech, Inc.
Hartmut Koeppen: Genentech, Inc.
Vishva M. Dixit: Genentech, Inc.

Nature, 2004, vol. 429, issue 6987, 86-92

Abstract: Abstract COP1 (constitutively photomorphogenic 1) is a RING-finger-containing protein that functions to repress plant photomorphogenesis, the light-mediated programme of plant development. Mutants of COP1 are constitutively photomorphogenic, and this has been attributed to their inability to negatively regulate the proteins LAF1 (ref. 1) and HY5 (ref. 2). The role of COP1 in mammalian cells is less well characterized3. Here we identify the tumour-suppressor protein p53 as a COP1-interacting protein. COP1 increases p53 turnover by targeting it for degradation by the proteasome in a ubiquitin-dependent fashion, independently of MDM2 or Pirh2, which are known to interact with and negatively regulate p53. Moreover, COP1 serves as an E3 ubiquitin ligase for p53 in vitro and in vivo, and inhibits p53-dependent transcription and apoptosis. Depletion of COP1 by short interfering RNA (siRNA) stabilizes p53 and arrests cells in the G1 phase of the cell cycle. Furthermore, we identify COP1 as a p53-inducible gene, and show that the depletion of COP1 and MDM2 by siRNA cooperatively sensitizes U2-OS cells to ionizing-radiation-induced cell death. Overall, these results indicate that COP1 is a critical negative regulator of p53 and represents a new pathway for maintaining p53 at low levels in unstressed cells.

Date: 2004
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature02514 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:429:y:2004:i:6987:d:10.1038_nature02514

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature02514

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().