Linked Life Data

16652378

Source:http://linkedlifedata.com/resource/pubmed/id/16652378

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-5-22
pubmed:abstractText
Phosphorylation of proteins on serine or threonine residues that immediately precede proline (pSer/Thr-Pro) is a central signaling mechanism in cell proliferation and transformation. Recent studies indicate that certain pSer/Thr-Pro motifs in native proteins exist in two completely distinct conformations, cis and trans, whose conversion is markedly slowed down upon phosphorylation, but specifically catalyzed by the peptidyl-prolyl cis/trans isomerase Pin1. Importantly, such Pin1-catalyzed conformational changes can have profound effects on the function of many phosphorylation signaling pathways, thereby playing an important role in various cellular processes. Moreover, increasing evidence indicates that aberrant Pin1 function plays an important role in the pathogenesis of some human diseases. Notably, Pin1 is not only overexpressed in a large number of human cancers, but also is an excellent prognostic marker in some cancers. Furthermore, Pin1 overexpression can function as a critical catalyst that amplifies multiple oncogenic signaling pathways during oncogenesis. Moreover, Pin1 overexpression causes cell transformation, centrosome amplification, genomic instability, and tumor development. In contrast, Pin1 knockout in mice prevents certain oncogenes from inducing tumors and Pin1 inhibition in cancer cells suppresses their cell proliferation, transformed phenotype and tumorigenicity in nude mice as well as increases the response to other anticancer agents. These results suggest that Pin1-mediated postphosphorylation regulation may provide a unique opportunity for disrupting oncogenic pathways, and thereby represent an appealing target for novel anticancer therapies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0899-1987
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
397-402
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Targeting carcinogenesis: a role for the prolyl isomerase Pin1?
pubmed:affiliation
Department of Medicine, Cancer Biology Program, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural