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The p53‐inducible E3 ubiquitin ligase p53RFP induces p53‐dependent apoptosis
Author(s) -
Huang Jun,
Xu Liang-Guo,
Liu Ting,
Zhai Zhonghe,
Shu Hong-Bing
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.09.105
Subject(s) - ubiquitin ligase , ubiquitin , ring finger , ring finger domain , microbiology and biotechnology , ubiquitin protein ligases , parkin , ubiquitin conjugating enzyme , inhibitor of apoptosis domain , apoptosis , biology , mdm2 , dna ligase , caspase , programmed cell death , biochemistry , gene , transcription factor , zinc finger , medicine , disease , pathology , parkinson's disease
Recently, it has been shown that really interesting new gene (RING)–in between ring finger (IBR)–RING domain‐containing proteins, such as Parkin and Parc, are E3 ubiquitin ligases and are involved in regulation of apoptosis. In this report, we show that p53‐inducible RING‐finger protein (p53RFP), a p53‐inducible E3 ubiquitin ligase, induces p53‐dependent but caspase‐independent apoptosis. p53RFP contains an N‐terminal RING–IBR–RING domain and an uncharacterized, evolutionally highly conserved C‐terminal domain. p53RFP interacts with E2 ubiquitin‐conjugating enzymes UbcH7 and UbcH8 but not with UbcH5, and this interaction is mediated through the RING–IBR–RING domain of p53RFP. Interestingly, the conserved C‐terminal domain of p53RFP is required and sufficient for p53RFP‐mediated apoptosis, suggesting p53RFP‐mediated apoptosis does not require its E3 ubiquitin ligase activity. Together with a recent report showing that p53RFP is involved in ubiquitination and degradation of p21, a p53 downstream protein promoting growth arrest and antagonizing apoptosis, our findings suggest that p53RFP is involved in switching a cell from p53‐mediated growth arrest to apoptosis.