title: RNF125 is a ubiquitin-protein ligase that promotes p53 degradation.
abstract: OBJECTIVE
  Although early studies show that Mdm2 is the primary E3 ubiquitin ligase for the p53 tumor suppressor, an increasing amount of data suggests that p53 ubiquitination and degradation are more complex than once thought. Here, we investigated the role of RNF125, a non-Mdm2 ubiquitin-protein ligase, in the regulation of p53.
  
  
  RESULTS
  RNF125 physically interacted with p53 in exogenous/endogenous co-immunoprecipitation (IP) and GST-pull down assay, and a C72/75A mutation of RNF125 did not interfere with this interaction. Expression of RNF125 decreased the level of p53 in a dose-dependent manner, whereas knockdown of RNF125 by RNA interference increased the level of p53. As shown by Western blotting and ubiquitin assay, RNF125 ubiquitinated p53 and targeted it for proteasome degradation. Furthermore, RNF125 repressed p53 functions including p53-dependent transactivation and growth inhibition.
  
  
  CONCLUSIONS
  Our data suggest that RNF125 negatively regulates p53 function through physical interaction and ubiquitin-mediated proteasome degradation.
authors.affiliation: Cancer Department of First Affiliated Hospital of Xinxiang Medical College, Xinxiang, Henna, China.
authors.forename: Liuzhong
authors.initials: L
authors.lastname: Yang
authors.forename: Bing
authors.initials: B
authors.lastname: Zhou
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Li
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Lu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Li
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Huo
authors.forename: Zhanhui
authors.initials: Z
authors.lastname: Miao
mesh_terms: D019943:Amino Acid Substitution; D049109:Cell Proliferation; D015536:Down-Regulation; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D007976:Leupeptins / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D059748:Proteolysis / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D007976:Leupeptins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; C551868:RNF125 protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde