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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
36
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pubmed:dateCreated |
2009-8-31
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pubmed:abstractText |
The cis-trans peptidylprolyl isomerase Pin1 plays a critical role in regulating a subset of phosphoproteins by catalyzing conformational changes on the phosphorylated Ser/Thr-Pro motifs. The phosphorylation-directed ubiquitination is one of the major mechanisms to regulate the abundance of p27(Kip1). In this study, we demonstrate that Pin1 catalyzes the cis-trans conformational changes of p27(Kip1) and further mediates its stability through the polyubiquitination mechanism. Our results show that the phosphorylated Thr-187-Pro motif in p27(Kip1) is a key Pin1-binding site. In addition, NMR analyses show that this phosphorylated Thr-187-Pro site undergoes conformational change catalyzed by Pin1. Moreover, in Pin1 knock-out mouse embryonic fibroblasts, p27(Kip1) has a shorter lifetime and displays a higher degree of polyubiquitination than in Pin1 wild-type mouse embryonic fibroblasts, suggesting that Pin1 plays a critical role in regulating p27(Kip1) degradation. Additionally, Pin1 dramatically reduces the interaction between p27(Kip1) and Cks1, possibly via isomerizing the cis-trans conformation of p27(Kip1). Our study thus reveals a novel regulatory mechanism for p27(Kip1) stability and sheds new light on the biological function of Pin1 as a general regulator of protein stability.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CDC2-CDC28 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CKS1B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1b protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cks1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/NIMA-interacting peptidylprolyl...,
http://linkedlifedata.com/resource/pubmed/chemical/Peptidylprolyl Isomerase,
http://linkedlifedata.com/resource/pubmed/chemical/Threonine
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
4
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pubmed:volume |
284
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
23980-8
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pubmed:dateRevised |
2010-9-7
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pubmed:meshHeading |
pubmed-meshheading:19584057-Amino Acid Motifs,
pubmed-meshheading:19584057-Animals,
pubmed-meshheading:19584057-CDC2-CDC28 Kinases,
pubmed-meshheading:19584057-Carrier Proteins,
pubmed-meshheading:19584057-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:19584057-Cyclin-Dependent Kinases,
pubmed-meshheading:19584057-Embryo, Mammalian,
pubmed-meshheading:19584057-Fibroblasts,
pubmed-meshheading:19584057-HeLa Cells,
pubmed-meshheading:19584057-Humans,
pubmed-meshheading:19584057-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:19584057-Mice,
pubmed-meshheading:19584057-Mice, Knockout,
pubmed-meshheading:19584057-Peptidylprolyl Isomerase,
pubmed-meshheading:19584057-Phosphorylation,
pubmed-meshheading:19584057-Protein Stability,
pubmed-meshheading:19584057-Threonine,
pubmed-meshheading:19584057-Ubiquitination
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pubmed:year |
2009
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pubmed:articleTitle |
Pin1 catalyzes conformational changes of Thr-187 in p27Kip1 and mediates its stability through a polyubiquitination process.
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pubmed:affiliation |
Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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