Linked Life Data

15604270

Source:http://linkedlifedata.com/resource/pubmed/id/15604270

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2004-12-17
pubmed:abstractText
Hypoxia-inducible factor (HIF)-1, a heterodimeric transcription factor composed of HIF-1alpha and HIF-1beta subunits coordinates pathophysiologic responses toward decreased oxygen availability. It is now appreciated that enhanced protein translation of HIF-1alpha under normoxia accounts for an alternative regulatory circuit to activate HIF-1 by hormones, growth factors, or cytokines such as tumor necrosis factor alpha (TNF-alpha). Here, we aimed at understanding molecular details of HIF-1alpha translation in response to TNF-alpha. In tubular LLC-PK(1) cells, activation of nuclear factor kappaB (NFkappaB) by TNF-alpha resulted in HIF-1alpha protein synthesis as determined by [(35)S]methionine pulse experiments. Protein synthesis was attenuated by blocking NFkappaB, phosphatidylinositol 3'-kinase (PI3k), and mitogen-activated protein kinase (MAPK). Use of a dicistronic reporter with the HIF-1alpha 5'-untranslated region (5'UTR) between two coding regions indicated that TNF-alpha promoted an internal ribosome entry site (IRES) rather than a cap-dependent translation. IRES-mediated translation required the functional integrity of the NFkappaB, PI3k, and MAPK signaling pathways. Although no signal cross-talk was noticed between NFkappaB, PI3k, and MAPK signaling, these pathways are needed to up-regulate the anti-apoptotic target protein Bcl-2 by TNF-alpha. Expression of Bcl-2 provoked not only IRES-dependent translation but also HIF-1alpha protein synthesis. We conclude that Bcl-2 functions as an important determinant in facilitating HIF-1alpha protein expression by TNF-alpha via an IRES-dependent translational mechanism. These observations suggest a link between Bcl-2 and HIF-1alpha expression, a situation with potential relevance to cancer biology.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9041-8
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Functional integrity of nuclear factor kappaB, phosphatidylinositol 3'-kinase, and mitogen-activated protein kinase signaling allows tumor necrosis factor alpha-evoked Bcl-2 expression to provoke internal ribosome entry site-dependent translation of hypoxia-inducible factor 1alpha.
pubmed:affiliation
Department of Cell Biology, Faculty of Biology, University of Kaiserslautern, Kaiserslautern, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't