Linked Life Data

10383134

Source:http://linkedlifedata.com/resource/pubmed/id/10383134

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1999-7-19
pubmed:abstractText
Cell cycle progression requires the proteasome-mediated degradation of key regulatory proteins such as cyclins, cyclin-dependent kinase inhibitors, and anaphase-inhibitory proteins. Given the central role of the proteasome in the destruction of these proteins, proteasome inhibition has been proposed as a possible cancer therapy. We report here that dihydroeponemycin, an analogue of the antitumor and antiangiogenic natural product eponemycin, selectively targets the 20S proteasome. Dihydroeponemycin covalently modifies a subset of catalytic proteasomal subunits, binding preferentially to the IFN-gamma-inducible subunits LMP2 and LMP7. Moreover, the three major peptidolytic activities of the proteasome are inhibited by dihydroeponemycin at different rates. In addition, dihydroeponemycin-mediated proteasome inhibition induces a spindle-like cellular morphological change and apoptosis. These results validate the proteasome as a target for antitumor pharmacological intervention and are relevant for the design of novel chemotherapeutic strategies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2798-801
pubmed:dateRevised
2008-11-20
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Eponemycin exerts its antitumor effect through the inhibition of proteasome function.
pubmed:affiliation
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520-8103, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't