A functional link between housekeeping selenoproteins and phase II enzymes.
Sec (selenocysteine) is biosynthesized on its tRNA and incorporated into selenium-containing proteins (selenoproteins) as the 21st amino acid residue. Selenoprotein synthesis is dependent on Sec tRNA and the expression of this class of proteins can be modulated by altering Sec tRNA expression. The gene encoding Sec tRNA (Trsp) is a single-copy gene and its targeted removal in liver demonstrated that selenoproteins are essential for proper function wherein their absence leads to necrosis and hepatocellular degeneration. In the present study, we found that the complete loss of selenoproteins in liver was compensated for by an enhanced expression of several phase II response genes and their corresponding gene products. The replacement of selenoprotein synthesis in mice carrying mutant Trsp transgenes, wherein housekeeping, but not stress-related selenoproteins are expressed, led to normal expression of phase II response genes. Thus the present study provides evidence for a functional link between housekeeping selenoproteins and phase II enzymes.
Sengupta
Aniruddha
A
Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, CCR, NCI, NIH, Bethesda, MD 20892, USA.
Carlson
Bradley A
BA
Weaver
James A
JA
Novoselov
Sergey V
SV
Fomenko
Dmitri E
DE
Gladyshev
Vadim N
VN
Hatfield
Dolph L
DL
D000818:Animals; D030801:Animals, Genetically Modified; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012345:RNA, Transfer, Amino Acid-Specific / Q000235:genetics / Q000378:metabolism; D012362:RNA, Transfer, Ser / Q000378:metabolism; D020218:Response Elements / Q000502:physiology*; D051140:Selenoproteins / Q000378:metabolism*; D015854:Up-Regulation
D012345:RNA, Transfer, Amino Acid-Specific; D012362:RNA, Transfer, Ser; D051140:Selenoproteins; C036928:tRNA, selenocysteine-