Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
36
pubmed:dateCreated
2009-8-31
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
284
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23980-8
pubmed:dateRevised
2010-9-7
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
pubmed:year
2009
pubmed:articleTitle
Pin1 catalyzes conformational changes of Thr-187 in p27Kip1 and mediates its stability through a polyubiquitination process.
pubmed:affiliation
Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't