Induction of a SSAT isoform in response to hypoxia or iron deficiency and its protective effects on cell death.
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.
Kim
Kyuheun
K
Department of Physiology, Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea.
Ryu
Ji-Hye
JH
Park
Jong-Wan
JW
Kim
Myung-Suk
MS
Chun
Yang-Sook
YS
D000123:Acetyltransferases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004790:Enzyme Induction; D006801:Humans; D007501:Iron / Q000502:physiology*; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D007501:Iron; D007527:Isoenzymes; D012333:RNA, Messenger; D000099228:Diamine N-Acetyltransferase