title: Skp2 Inhibitors: Novel Anticancer Strategies.
abstract: Skp2 is frequently overexpressed in many human cancers and plays a key role in tumorigenesis. As a component of the SCFSkp2ubiquitin E3 ligase complex, Skp2 is responsible for recruiting substrate proteins for their ubiquitination and subsequent degradation by the 26S proteasome. Thus, Skp2 promotes the cell cycle by down-regulating cell cycle proteins such as the tumor suppressor p27. Alternatively, Skp2 suppresses p53-dependent apoptosis by outcompeting p53 for binding to p300, thereby perturbing p300-mediated p53 acetylation and stabilization. Taken together, inhibition of Skp2 functions (either proteolytic function or non-proteolytic function) is emerging as a promising and novel anti-cancer strategy. In the present review, we highlight the development of Skp2 inhibitors with different mechanisms of action.
authors.forename: Yeongju
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Departments of Chemistry and Advanced Material Science, Pohang University of Science and Technology, Pohang 37673, South Korea.
authors.forename: Hyun-Suk
authors.initials: HS
authors.lastname: Lim
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002264:Carboxylic Acids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D006801:Humans; D006873:Hydroquinones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D006873:Hydroquinones; D044786:S-Phase Kinase-Associated Proteins; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease