title: Ubiquitin E3 ligase UHRF1 regulates p53 ubiquitination and p53-dependent cell apoptosis in clear cell Renal Cell Carcinoma.
abstract: Ubiquitin-like with PHD and RING finger domain 1 (UHRF1) is a multi-domain ubiquitin E3 ligase that plays critical roles in regulation of DNA methylation and histone ubiquitination. In this study, we found UHRF1 is frequently overexpressed in human clear cell Renal Cell Carcinoma (ccRCC) tissues both at mRNA and protein levels. We showed that UHRF1 directly interacts with p53 both in vivo and in vitro. A new domain (PD) in UHRF1 was required for interaction with p53. We found that UHRF1 down-regulates p53 transactivation activity which was depends on the ubiquitin E3 ligase function. UHRF1 can promote non-degradative ubiquitination of p53, suppress p53 pathway activation and p53-dependent apoptosis in ccRCC cells. Together, our study suggests that UHRF1, which overexpressed ccRCC, may act as a p53 regulator, suppress p53 pathway activation and help ccRCC cells to escape from p53-dependent apoptosis.
authors.affiliation: Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China.
authors.forename: Jingtao
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China; Department of Urology, Inner Mongolia Autonomous Region Peoples Hospital, Hohhot 010017, Inner Mongolia, China.
authors.forename: Ren
authors.initials: R
authors.lastname: Mo
authors.affiliation: Department of Pathology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China.
authors.forename: Shaofei
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Pathology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zang
authors.affiliation: Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China. Electronic address: joelwg@sina.com.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China. Electronic address: jief67@sina.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Fan
mesh_terms: D017209:Apoptosis; D022762:CCAAT-Enhancer-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Apoptosis; Ubiquitination; ccRCC; p53