Recent human clinical trials have demonstrated a cancer-chemopreventive effect of dietary selenium, and additional trials are underway. Evidence has also accumulated for the role of selenium in reducing cancer incidence in animal model systems. However, the molecular basis for chemoprevention by this essential trace element remains unknown. This project will employ biochemical and genetic techniques and mouse model systems to functionally characterize a recently identified 15 kDa selenoprotein and to determine its role in cancer prevention. Preliminary studies suggest that the effect of selenium in cancer may be mediated by this selenoprotein. Data are presented that indicate that the 15 kDa protein gene locus is deleted and expression of the selenoprotein is altered in certain cancers. The human selenoprotein gene has two polymorphic sites within 3'-UTR that exhibit ethnic distribution and influence incorporation of selenocysteine into protein. The two human alleles respond differentially to selenium supplementation. Preliminary data also show an association between the 15 kDa selenoprotein and UDP-glucose glycoprotein glucosyltransferase in the endoplasmic reticulum of mammalian cells implicating the selenoprotein in the quality control of protein folding. Proposed studies include 1) characterization of the 15 kDa protein function using a combination of genetic and biochemical approaches, with emphasis on elucidating the role of the selenoprotein in regulation of protein folding; 2) characterization of the consequences of 15 kDa protein deficiency in knockout mice; and 3) testing the hypothesis that increased expression of the 15 kDa protein may protect against developing cancer in mice.
| Peters, Kristin M; Carlson, Bradley A; Gladyshev, Vadim N et al. (2018) Selenoproteins in colon cancer. Free Radic Biol Med 127:14-25 |
| Carlson, Bradley A; Lee, Byeong Jae; Tsuji, Petra A et al. (2018) Selenocysteine tRNA[Ser]Sec, the Central Component of Selenoprotein Biosynthesis: Isolation, Identification, Modification, and Sequencing. Methods Mol Biol 1661:43-60 |
| Lee, Sang-Goo; Mikhalchenko, Aleksei E; Yim, Sun Hee et al. (2017) Naked Mole Rat Induced Pluripotent Stem Cells and Their Contribution to Interspecific Chimera. Stem Cell Reports 9:1706-1720 |
| Lee, Sang-Goo; Kaya, Alaattin; Avanesov, Andrei S et al. (2017) Age-associated molecular changes are deleterious and may modulate life span through diet. Sci Adv 3:e1601833 |
| Ke, Zhonghe; Mallik, Pramit; Johnson, Adam B et al. (2017) Translation fidelity coevolves with longevity. Aging Cell 16:988-993 |
| Moskalev, Alexey; Anisimov, Vladimir; Aliper, Aleksander et al. (2017) A review of the biomedical innovations for healthy longevity. Aging (Albany NY) 9:7-25 |
| Podolskiy, Dmitriy I; Lobanov, Alexei V; Kryukov, Gregory V et al. (2016) Analysis of cancer genomes reveals basic features of human aging and its role in cancer development. Nat Commun 7:12157 |
| Tobe, Ryuta; Carlson, Bradley A; Huh, Jang Hoe et al. (2016) Selenophosphate synthetase 1 is an essential protein with roles in regulation of redox homoeostasis in mammals. Biochem J 473:2141-54 |
| Mariotti, Marco; Lobanov, Alexei V; Manta, Bruno et al. (2016) Lokiarchaeota Marks the Transition between the Archaeal and Eukaryotic Selenocysteine Encoding Systems. Mol Biol Evol 33:2441-53 |
| Podolskiy, Dmitriy I; Gladyshev, Vadim N (2016) Intrinsic Versus Extrinsic Cancer Risk Factors and Aging. Trends Mol Med 22:833-834 |
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