SKP2


SKP2

S-phase kinase-associated protein 2 (p45), also known as SKP2, is a human gene. [cite web | title = Entrez Gene: SKP2 S-phase kinase-associated protein 2 (p45)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6502| accessdate = ]

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-boxcite journal|journal=Cell|title=SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box.|author= Bai et al.|date=1996|volume=86|issue=2|pages=263-74] . The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box protein|F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifsKipreos ET, Pagano M. (2000). The F-box protein family. "Genome Biol" 1(5):REVIEWS3002. PMID 11178263 ] . The protein encoded by this gene belongs to the Fbls class; in addition to an F-box, this protein contains 10 tandem leucine-rich repeats. This protein is an essential element of the cyclin A-CDK2 S-phase kinase. It specifically recognizes phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also referred to as p27 or KIP1) predominantly in S phase and interacts with S-phase kinase-associated protein 1 (SKP1 or p19) [cite journal|journal=Nat Cell Biol|title=SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27.|author=Carrano et al|volume=1|issue=4|pages=193-9] [cite journal|journal=Curr Biol|title=p27(Kip1) ubiquitination and degradation is regulated by the SCF(Skp2) complex through phosphorylated Thr187 in p27.|author=Tsvetkov et al|volume=9|issue=12|page=661-4] . In addition, this gene is established as a protooncogene causally involved in the pathogenesis of lymphomas [cite journal|journal=Proc Natl Acad Sci U S A|title=Role of the F-box protein Skp2 in lymphomagenesis.|author=Latres et al|volume=98|issue=5|pages=2515-20] . Alternative splicing of this gene generates 2 transcript variants encoding different isoforms.

References

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