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Induction of a SSAT isoform in response to hypoxia or iron deficiency and its protective effects on cell death

Cited 20 time in Web of Science Cited 20 time in Scopus
Authors
Kim, Kyuheun; Ryu, Ji-Hye; Park, Jong-Wan; Kim, Myung-Suk; Chun, Yang-Sook
Issue Date
2006-04-23
Publisher
Elsevier
Citation
Biochem Biophys Res Commun. 2005 May 27;331(1):78-85.
Keywords
Acetyltransferases/biosynthesis/genetics/*physiologyAlternative SplicingAmino Acid SequenceCell HypoxiaCell Line, TumorCell ProliferationCell SurvivalEnzyme InductionHumansIron/*physiologyIsoenzymes/biosynthesis/genetics/physiologyMolecular Sequence DataNeoplasms/*enzymologyRNA, Messenger/metabolism
Abstract
Spermidine/spermine N(1)-acetyltransferase (SSAT) is the key enzyme with regard to the maintenance of intracellular polyamine levels. It is an inducible enzyme, which may participate in adaptive responses to environmental stress. However, little is known regarding its responses to oxygen or nutrient deficiencies. Using microarray assays, we discovered that SSAT was enhanced under both oxygen- and iron-deficient conditions. However, RT-PCR revealed that the SSAT mRNA was not induced; rather, an mRNA variant was newly expressed. In this variant, the splicing-in of 110 bases induces early termination, generating a truncated isoform which lacks catalytic motifs. The variant expression occurs in other cancer cells and was irrelevant to both hypoxia-inducible factor 1 and to the redox state. We attempted to determine its role, using stable cell-lines. The expressed isoform was found to promote cell survival under iron-deficient conditions and blocked the cleavage of poly(ADP-ribose) polymerase. This isoform may contribute to the progression of tumors of a more malignant phenotype under poor conditions and may constitute a potential target for anticancer therapy.
ISSN
0006-291X (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15845361

http://hdl.handle.net/10371/39196
DOI
https://doi.org/10.1016/j.bbrc.2005.03.121
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College of Medicine/School of Medicine (의과대학/대학원)Molecular and Genomic Medicine (분자유전체의학전공)Journal Papers (저널논문_분자유전체의학전공)
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