Identification and characterization of two novel isoforms of Pirh2 ubiquitin ligase that negatively regulate p53 independent of RING finger domains.

ABSTRACT: Pirh2 is a newly identified E3 ubiquitin ligase known to inhibit tumor suppressor p53 function via ubiquitination and proteasomal degradation. We have identified two novel Pirh2 splice variants that encode different Pirh2 isoforms and named these Pirh2B and Pirh2C. Accordingly, the full-length protein is now classified as isoform Pirh2A. The central region of Pirh2 harbors a RING finger domain that is critical for its ubiquitin ligase function. The Pirh2B isoform lacks amino acids 171-179, whereas Pirh2C is missing C-terminal amino acids 180-261, which for each isoform results in a RING domain deletion and the abrogation of ubiquitin ligase activity. Our findings further indicate that the Pirh2B isoform but not the Pirh2C isoform is capable of binding to Pirh2A, suggesting that the C-termi

SUBMITTER: Corcoran CA 

PROVIDER: S-EPMC2755920 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature