Linked Life Data

9988751

Source:http://linkedlifedata.com/resource/pubmed/id/9988751

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1999-3-18
pubmed:abstractText
Iron-regulatory proteins 1 and 2 (IRP1 and IRP2) are RNA-binding proteins that post-transcriptionally regulate the expression of mRNAs that code for proteins involved in the maintenance of iron and energy homeostasis. Here we show that hypoxia differentially regulates the RNA binding activities of IRP1 and IRP2 in human 293 and in mouse Hepa-1 cells. In contrast to IRP1, where hypoxic exposure decreases IRP1 RNA binding activity, hypoxia increases IRP2 RNA binding activity. The hypoxic increase in IRP2 RNA binding activity results from increased IRP2 protein levels. Cobalt, which mimics hypoxia by activation of hypoxia-inducible factor 1 (HIF-1), also increases IRP2 protein levels; however, cobalt-induced IRP2 lacks RNA binding activity. Addition of a reductant to cobalt-treated extracts restored IRP2 RNA binding activity. Hypoxic activation of IRP2 is not because of an increase in transcriptional activation by HIF-1, because IRP2 accumulates in Hepa-1 cells lacking a functional HIF-1beta subunit, nor is it because of an increase in IRP2 mRNA stability. Rather, our data indicate that hypoxia increases IRP2 levels by a post-translational mechanism involving protein stability. Differential regulation of IRP1 and IRP2 during hypoxia may regulate specific IRP target mRNAs whose expression is required for hypoxic adaptation. Furthermore, these data imply mechanistic parallels between the hypoxia-induced post-transcriptional regulation of IRP2 and HIF-1alpha.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5047-52
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Hypoxia post-translationally activates iron-regulatory protein 2.
pubmed:affiliation
Eccles Program in Human Molecular Biology and Genetics and the Department of Medicine, Division of Hematology-Oncology, University of Utah, Salt Lake City, Utah 84112, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't