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http://purl.uniprot.org/citations/18006823http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18006823http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18006823http://www.w3.org/2000/01/rdf-schema#comment"The cyclin-dependent kinase inhibitor p27(Kip1) is degraded in late G(1) phase by the ubiquitin-proteasome pathway, allowing cells to enter S phase. Due to accelerated degradation of p27(Kip1), various human cancers express low levels of p27(Kip1) associated with poor prognosis. S-phase kinase-associated protein 2, the F-box protein component of an SCF ubiquitin ligase complex, is implicated in degradation of p27(Kip1) during S-G(2) phases. Recently, Kip1 ubiquitination-promoting complex has been reported as another ubiquitin ligase that targets cytoplasmic p27(Kip1) exported from the nucleus in G(0)-G(1) phases. Here, we identified a RING-H2-type ubiquitin ligase, Pirh2, as a p27(Kip1)-interacting protein. Endogenous Pirh2 physically interacted with endogenous p27(Kip1) in mammalian cells. Pirh2 directly ubiquitinated p27(Kip1) in an intact RING finger domain-dependent manner in vivo, as well as in vitro. Ablation of endogenous Pirh2 by small interfering RNA increased the steady-state level of p27(Kip1) and decelerated p27(Kip1) turnover. Depletion of Pirh2 induced accumulation of p27(Kip1) in both the nucleus and cytoplasm. Pirh2 expression was induced from late G(1)-S phase, whereas p27(Kip1) was decreased in synchronization with accumulation of Pirh2. Furthermore, reduction of Pirh2 resulted in an impairment of p27(Kip1) degradation and an inhibition of cell cycle progression at G(1)-S transition in a p53-independent manner. Overall, the results indicate that Pirh2 acts as a negative regulator of p27(Kip1) function by promoting ubiquitin-dependent proteasomal degradation."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.org/dc/terms/identifier"doi:10.1158/0008-5472.can-07-2033"xsd:string
http://purl.uniprot.org/citations/18006823http://purl.org/dc/terms/identifier"doi:10.1158/0008-5472.can-07-2033"xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/author"Oda T."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/author"Oda T."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/author"Abe K."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/author"Abe K."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/author"Kikuchi H."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/author"Kikuchi H."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/author"Kitagawa M."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/author"Kitagawa M."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/author"Isobe T."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/author"Isobe T."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/author"Hattori T."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/author"Hattori T."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/author"Kitagawa K."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/author"Kitagawa K."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/author"Uchida C."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/author"Uchida C."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/name"Cancer Res."xsd:string
http://purl.uniprot.org/citations/18006823http://purl.uniprot.org/core/name"Cancer Res."xsd:string