Source:http://linkedlifedata.com/resource/pubmed/id/18006823
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
22
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pubmed:dateCreated |
2007-11-16
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RCHY1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/TP53 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1538-7445
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
67
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10789-95
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:18006823-Animals,
pubmed-meshheading:18006823-Cell Cycle,
pubmed-meshheading:18006823-Cell Line, Tumor,
pubmed-meshheading:18006823-Cell Nucleus,
pubmed-meshheading:18006823-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:18006823-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:18006823-Humans,
pubmed-meshheading:18006823-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:18006823-Mice,
pubmed-meshheading:18006823-Mice, Transgenic,
pubmed-meshheading:18006823-Protein Binding,
pubmed-meshheading:18006823-Protein Kinase Inhibitors,
pubmed-meshheading:18006823-RNA, Small Interfering,
pubmed-meshheading:18006823-Tumor Suppressor Protein p53,
pubmed-meshheading:18006823-Ubiquitin,
pubmed-meshheading:18006823-Ubiquitin-Protein Ligases
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pubmed:year |
2007
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pubmed:articleTitle |
Pirh2 promotes ubiquitin-dependent degradation of the cyclin-dependent kinase inhibitor p27Kip1.
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pubmed:affiliation |
Department of Biochemistry 1, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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