Pirh2 RING-finger E3 ubiquitin ligase: its role in tumorigenesis and cancer therapy.
The ubiquitin-dependent proteasome system plays a critical role in many cellular processes and pathogenesis of various human diseases, including cancer. Although there are a large number of E3 ubiquitin ligases, the majority are RING-finger type E3s. Pirh2, a target of p53 transcription factor, contains a highly conserved C(3)H(2)C(3) type RING domain. Importantly, Pirh2 was found to regulate a group of key factors dedicated to the DNA damage response, such as p53, p73, PolH, and c-Myc. Interestingly, Pirh2 was upregulated or downregulated in different types of cancers. These suggest that Pirh2 is implicated in either promoting or suppressing tumor progression in a tissue-dependent manner. This review will focus on the major findings in these studies and discuss the potential to explore Pirh2 as a cancer therapeutic target.
Comparative Oncology Laboratory, University of California, Davis, CA 95616, USA.
Yong-Sam
YS
Jung
Yingjuan
Y
Qian
Xinbin
X
Chen
D000595:Amino Acid Sequence; D000818:Animals; D002471:Cell Transformation, Neoplastic; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy*; D011485:Protein Binding; D051736:Proto-Oncogene Proteins c-mdm2 / Q000502:physiology; D054829:RING Finger Domains; D017386:Sequence Homology, Amino Acid; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000502:physiology*
D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2; C485369:RCHY1 protein, human; D044767:Ubiquitin-Protein Ligases