HAUSP, a deubiquitinating enzyme for p53, is polyubiquitinated, polyneddylated, and dimerized.
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.
Lee
Hye-Jin
HJ
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.
Kim
Myung-Sun
MS
Kim
Yu-Kyung
YK
Oh
Yu-Kyoung
YK
Baek
Kwang-Hyun
KH
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*
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