Linked Life Data

19177013

Source:http://linkedlifedata.com/resource/pubmed/id/19177013

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-2-13
pubmed:abstractText
Interest in HSP90 inhibitors has grown rapidly in the last decade. The heightened dependence of malignant cells on molecular chaperones to maintain multiple oncogenic signalling pathways gives HSP90 broad anticancer appeal. New HSP90-directed agents are continually emerging, several of which are under clinical evaluation. In parallel, dissection of the functional mechanism of the chaperone system has emphasised the importance of cochaperones that regulate HSP90. As we begin to fully elucidate the roles of these HSP90 accessory proteins, it is becoming increasingly clear that they too have potential as additional routes to disrupt chaperone activity. CDC37, a predominantly kinase client-associated cochaperone that promotes malignant transformation, has particular promise. Recently, we demonstrated that, similar to HSP90 inhibitors, siRNA-mediated CDC37 silencing caused the proteasomal degradation of kinase client proteins and inhibited the proliferation of cancer cells. Importantly, depleting CDC37 does not induce the unwanted, antiapoptotic heat shock response that is characteristic of pharmacologic HSP90 inhibition. Furthermore, CDC37 silencing sensitises cancer cells to HSP90 inhibitors by potentiating kinase client depletion and the induction of apoptosis, suggesting that simultaneously modulating HSP90 and CDC37 could be beneficial. Here we discuss the therapeutic possibilities of targeting CDC37 for cancer treatment in light of recent significant findings.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1551-4005
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
362-72
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Targeting CDC37: an alternative, kinase-directed strategy for disruption of oncogenic chaperoning.
pubmed:affiliation
Signal Transduction and Molecular Pharmacology Team, Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't