title: HAUSP, a deubiquitinating enzyme for p53, is polyubiquitinated, polyneddylated, and dimerized.
abstract: The tumor suppressor protein p53 is ubiquitinated and neddylated by MDM2 and then degraded by 26S proteasome. However, p53 is stabilized by the HAUSP (Herpes-virus-associated ubiquitin-specific protease) deubiquitinating enzyme. In this study, we discovered that rat HAUSP (rHAUSP) is polyubiquitinated, polyneddylated, and dimerized using co-immunoprecipitation assays. This suggests that rHAUSP may function as a dimer or multimer and is also degraded through the proteasome-mediated degradation. Transfection of rHAUSP into RGC-Lac-Z cell line with the integrated p53 response element revealed that rHAUSP contributed to p53 stabilization, and a rHAUSP (C224S) mutant contributed to p53 destabilization in a dose-dependent manner.
authors.affiliation: Graduate School of Life Science and Biotechnology, Cell and Gene Therapy Research Institute, Pochon CHA University, CHA General Hospital, 605 Yeoksam 1-dong, Kangnam-Gu, Seoul 135-081, Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Myung-Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Yu-Kyung
authors.initials: YK
authors.lastname: Kim
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Baek
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D019281:Dimerization; D010450:Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011487:Protein Conformation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D051381:Rats; D014018:Tissue Distribution; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D014452:Ubiquitins; C497207:Mdm2 protein, mouse; C497208:Mdm2 protein, rat; D051736:Proto-Oncogene Proteins c-mdm2; D010450:Endopeptidases; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7; C504243:Usp7 protein, rat; D046988:Proteasome Endopeptidase Complex