Linked Life Data

17616671

Source:http://linkedlifedata.com/resource/pubmed/id/17616671

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2007-7-9
pubmed:abstractText
We have previously shown that trivalent arsenic (arsenite, As(3+)) is able to induce GADD45 alpha expression in human bronchial epithelial cells through activation of c-Jun NH(2)-terminal kinase and nucleolin-dependent mRNA stabilization. In the present report, we show that As(3+) is capable of inducing translation of the GADD45 alpha protein through a cap-independent, or rather, an internal ribosome entry site (IRES)-dependent mechanism. In growth-arrested cells, As(3+) elevated the GADD45 alpha protein level in a dose- and time-dependent manner which did not correlate with the GADD45 alpha mRNA expression. Pretreatment of the cells with rapamycin, an inhibitor for the cap-dependent translation machinery through the suppression of mTOR and p70S6 kinase, failed to affect the induction of the GADD45 alpha protein induced by As(3+). Sequence analysis revealed a potential IRES element in the 5'-untranslated region of the GADD45 alpha mRNA. This IRES element in the 5'-untranslated region of the GADD45 alpha mRNA is functional in mediating As(3+)-induced translation of the GADD45 alpha protein in a dicistronic reporter gene activity assay. Immunoprecipitation and proteomic studies suggest that As(3+) impairs the assembly of the cap-dependent initiating complex for general protein translation but increases the association of human elongation factor 2 and human heterogeneous nuclear ribonucleoprotin with this complex. Thus, these results suggest that in growth-arrested cells, As(3+) is still capable of inducing GADD45 alpha expression through an IRES-dependent translational regulation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6146-54
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17616671-Amino Acid Sequence, pubmed-meshheading:17616671-Arsenic, pubmed-meshheading:17616671-Base Sequence, pubmed-meshheading:17616671-Cell Cycle Proteins, pubmed-meshheading:17616671-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17616671-Genes, Reporter, pubmed-meshheading:17616671-Heterogeneous-Nuclear Ribonucleoproteins, pubmed-meshheading:17616671-Humans, pubmed-meshheading:17616671-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:17616671-Molecular Sequence Data, pubmed-meshheading:17616671-Nuclear Proteins, pubmed-meshheading:17616671-Promoter Regions, Genetic, pubmed-meshheading:17616671-RNA, Messenger, pubmed-meshheading:17616671-Ribosomal Protein S6 Kinases, 70-kDa, pubmed-meshheading:17616671-Ribosomes, pubmed-meshheading:17616671-Sequence Homology, Amino Acid
pubmed:year
2007
pubmed:articleTitle
Incorporation of an internal ribosome entry site-dependent mechanism in arsenic-induced GADD45 alpha expression.
pubmed:affiliation
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, West Verginia University, Morgantown, WV 26505, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural