Structure-expression relationships of the 15-kDa selenoprotein gene: Possible role of the protein in cancer etiology

Easwari Kumaraswamy, Andrey Malykh, Konstantin V. Korotkov, Sergei Kozyavkin, Yajun Hu, So Yeon Kwon, Mohamed E. Moustafa, Bradley A. Carlson, Marla J. Berry, Byeong J. Lee, Dolph L. Hatfield, Alan M. Diamond, Vadim N. Gladyshev

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

Selenium has been implicated in cancer prevention, but the mechanism and possible involvement of selenoproteins in this process are not understood. To elucidate whether the 15-kDa selenoprotein may play a role in cancer etiology, the complete sequence of the human 15-kDa protein gene was determined, and various characteristics associated with expression of the protein were examined in normal and malignant cells and tissues. The 51-kilobase pair gene for the 15-kDa selenoprotein consisted of five exons and four introns and was localized on chromosome 1p31, a genetic locus commonly mutated or deleted in human cancers. Two stemloop structures resembling selenocysteine insertion sequence elements were identified in the 3'-untranslated region of the gene, and only one of these was functional. Two alleles in the human 15-kDa protein gene were identified that differed by two single nucleotide polymorphic sites that occurred within the selenocysteine insertion sequence-like structures. These 3'-untranslated region polymorphisms resulted in changes in selenocysteine incorporation into protein and responded differently to selenium supplementation. Human and mouse 15-kDa selenoprotein genes manifested the highest level of expression in prostate, liver, kidney, testis, and brain, and the level of the selenoprotein was reduced substantially in a malignant prostate cell line and in hepatocarcinoma. The expression pattern of the 15-kDa protein in normal and malignant tissues, the occurfence of polymorphisms associated with protein expression, the role of selenium in differential regulation of polymorphisms, and the chromosomal location of the gene may be relevant to a role of this protein in cancer.

Original languageEnglish
Pages (from-to)35540-35547
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number45
DOIs
StatePublished - Nov 10 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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