Anti-RCHY1 (aa 1-100) polyclonal antibody

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.

HDAC2, one of the class I histone deacetylase regulates epigenetic landscape through histone modification. Because HDAC2 is overexpressed in many cancers, cancer therapeutics against HDAC2 have been developed. Here we show novel mechanism of HDAC2 regulation by E3 ligase RCHY1. We found inverse correlation RCHY1 and HDAC2 levels in tumor tissue from six independent dataset using meta-analysis. Ectopic expression of RCHY1 decreased the level of HDAC2 from cancer cells including p53 wildtype, mutant and null cells. In addition, HDAC2 was increased by RCHY1 knockdown. RCHY1 directly interacts with HDAC2. Ectopic expression of wild type but not RING mutant RCHY1 increased HDAC2 levels. These data provide an evidence that RCHY1 negatively regulates HDAC2. (C) 2019 Elsevier Inc. All rights reserved.