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Structure-expression relationships of the 15-kDa selenoprotein gene. Possible role of the protein in cancer etiology.
J Biol Chem. 2000 Nov 10; 275(45):35540-7.JB

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 stem-loop 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 occurrence 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.

Authors+Show Affiliations

Section on the Molecular Biology of Selenium, Basic Research Laboratory, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10945981

Citation

Kumaraswamy, E, et al. "Structure-expression Relationships of the 15-kDa Selenoprotein Gene. Possible Role of the Protein in Cancer Etiology." The Journal of Biological Chemistry, vol. 275, no. 45, 2000, pp. 35540-7.
Kumaraswamy E, Malykh A, Korotkov KV, et al. Structure-expression relationships of the 15-kDa selenoprotein gene. Possible role of the protein in cancer etiology. J Biol Chem. 2000;275(45):35540-7.
Kumaraswamy, E., Malykh, A., Korotkov, K. V., Kozyavkin, S., Hu, Y., Kwon, S. Y., Moustafa, M. E., Carlson, B. A., Berry, M. J., Lee, B. J., Hatfield, D. L., Diamond, A. M., & Gladyshev, V. N. (2000). Structure-expression relationships of the 15-kDa selenoprotein gene. Possible role of the protein in cancer etiology. The Journal of Biological Chemistry, 275(45), 35540-7.
Kumaraswamy E, et al. Structure-expression Relationships of the 15-kDa Selenoprotein Gene. Possible Role of the Protein in Cancer Etiology. J Biol Chem. 2000 Nov 10;275(45):35540-7. PubMed PMID: 10945981.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structure-expression relationships of the 15-kDa selenoprotein gene. Possible role of the protein in cancer etiology. AU - Kumaraswamy,E, AU - Malykh,A, AU - Korotkov,K V, AU - Kozyavkin,S, AU - Hu,Y, AU - Kwon,S Y, AU - Moustafa,M E, AU - Carlson,B A, AU - Berry,M J, AU - Lee,B J, AU - Hatfield,D L, AU - Diamond,A M, AU - Gladyshev,V N, PY - 2000/8/18/pubmed PY - 2001/2/28/medline PY - 2000/8/18/entrez SP - 35540 EP - 7 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 275 IS - 45 N2 - 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 stem-loop 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 occurrence 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/10945981/Structure_expression_relationships_of_the_15_kDa_selenoprotein_gene__Possible_role_of_the_protein_in_cancer_etiology_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=10945981 DB - PRIME DP - Unbound Medicine ER -