title: E3 ubiquitin ligase Hades negatively regulates the exonuclear function of p53.
abstract: Following DNA damage, p53 translocates to the cytoplasm and mitochondria, where it triggers transcription-independent apoptosis by binding to Bcl-2 family proteins. However, little is known about how this exonuclear function of p53 is regulated. Here, we identify and characterize a p53-interacting protein called Hades, an E3 ligase that interacts with p53 in the mitochondria. Hades reduces p53 stability via a mechanism that requires its RING-finger domain with ubiquitin ligase activity. Hades polyubiquitinates p53 in vitro independent of Mdm2 and targets a critical lysine residue in p53 (lysine 24) distinct from those targeted by Mdm2. Hades inhibits a p53-dependent mitochondrial cell death pathway by inhibiting p53 and Bcl-2 interactions. These findings show that Hades-mediated p53 ubiquitination is a novel mechanism for negatively regulating the exonuclear function of p53.
authors: Functional Genoproteome Research Centre, Konkuk University, Seoul, Korea.
authors: J H
authors: JH
authors: Jung
authors: S
authors: S
authors: Bae
authors: J Y
authors: JY
authors: Lee
authors: S R
authors: SR
authors: Woo
authors: H J
authors: HJ
authors: Cha
authors: Y
authors: Y
authors: Yoon
authors: K-S
authors: KS
authors: Suh
authors: S-J
authors: SJ
authors: Lee
authors: I-C
authors: IC
authors: Park
authors: Y-W
authors: YW
authors: Jin
authors: K-H
authors: KH
authors: Lee
authors: S
authors: S
authors: An
authors: J H
authors: JH
authors: Lee
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