Linked Life Data

19515556

Source:http://linkedlifedata.com/resource/pubmed/id/19515556

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2009-7-14
pubmed:abstractText
Hypoxia-inducible factor (HIF)-1alpha undergoes degradation under normoxia, which involves its proline hydroxylation and subsequent binding of proline-hydroxylated HIF-1alpha to the von Hippel-Lindau protein-Elongin B-Elongin C (VBC) complex. In this study, we designed and synthesized a series of peptides containing 556-575 residues of HIF-1alpha with modifications at the Pro-564 residue to inhibit the interaction between proline-hydroxylated HIF-1alpha and VBC. Employing a fluorescence polarization-based interaction assay, we evaluated inhibitory potency of these peptides and selected potent inhibitors. We then analyzed their effects in the cell level to show that the selected inhibitors induced HIF-1alpha stabilization in normoxic cells. Considering that proline hydroxylation of HIF-1alpha is routinely targeted for modulating the HIF pathway, our approach of using inhibitors against the interactions between HIF-1alpha and VBC would provide an alternative way of upregulating HIF-1 activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1464-3405
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4403-5
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
HIF-1alpha peptide derivatives with modifications at the hydroxyproline residue as activators of HIF-1alpha.
pubmed:affiliation
Life Sciences Research Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea. drahn@kist.re.kr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't