title: Dissecting roles of ubiquitination in the p53 pathway.
abstract: Posttranslational modification of proteins by mono- or polyubiquitination represents a central mechanism to modulate a wide range of cellular functions like protein stability, intracellular transport, protein interactions, and transcriptional activity. Analogous to other posttranslational modifications, ubiquitination is a reversible process counteracted by deubiquitinating enzymes (DUBs), which cleave the isopeptide linkage between protein substrate and the ubiquitin residue. The p53 tumor suppressor is a sequence-specific DNA-binding transcriptional factor that plays a central role in regulating growth arrest and apoptosis during the stress response. Notably, recent studies indicate that both the stability and the subcellular localization of p53 are tightly regulated by ubiquitination; p53 is mainly ubiquitinated by Mdm2 but other ubiquitin ligases such as ARF-BP1/HectH9/MULE are also involved in p53 regulation in vivo. Moreover, a deubiquitinase HAUSP was initially identified in p53 deubiquitination but more recent studies showed that both Mdm2 and Mdmx are also bona fide substrates of HAUSP. In this article, we review our latest understanding of ubiquitination in modulating the p53 tumor suppression pathway.
authors.affiliation: Institute for Cancer Genetics and Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University 1130 St. Nicholas Ave, New York, NY 10032, USA.
authors.forename: J
authors.initials: J
authors.lastname: Shan
authors.forename: C
authors.initials: C
authors.lastname: Brooks
authors.forename: N
authors.initials: N
authors.lastname: Kon
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Gu
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D016159:Tumor Suppressor Protein p53; D020727:ADP-Ribosylation Factors