Regulation by SREBP-2 defines a potential link between isoprenoid and adenosylcobalamin metabolism

被引：20

作者：

Murphy, Charlotte ^{[1
]}

Murray, Ann Marie ^{[1
]}

Meaney, Steve ^{[1
]}

Gafvels, Mats ^{[1
]}

机构：

[1] Karolinska Univ Hosp, Karolinska Inst, Dept Lab Med, Div Clin Chem, S-14186 Huddinge, Sweden

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2007年 / 355卷 / 02期

关键词：

mevalonate kinase; cob(I)alamin adenotransferase; cholesterol; SREBP; atorvastatin; TRANSCRIPTION FACTOR; NF-Y; PROMOTER; BINDING; PATHWAY; GENES; MICE;

D O I：

10.1016/j.bbrc.2007.01.155

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mevalonate kinase (MVK) catalyses an early step in cholesterol biosynthesis converting mevalonate to phosphomevalonate. Cob(I)alamin adenosyltransferase (MMAB) converts cob(I)alamin to adenosylcobalamin, functionally required for mitochondrial methylmalonyl-CoA mutase activity and succinyl-CoA formation. These two synthenic genes are found in a head-to-head formation on chromosome 12 in man and chromosome 5 in mouse. The 330 bp intergenic region showed several conserved NF-Y sites indicative of potential bidirectional regulatory SREBP synergism. Both MVK and MMAB appear to be regulated in a similar manner, to a large extent by SREBP-2, since their tissue expression pattern was similar and both genes were suppressed by an excess of cholesterol as well as SREBP-2 knockdown. Statin treatment in mice upregulated both Mvk and Mmab mRNA levels indicating that this treatment may be useful in inborn errors of cblB complementation associated with methylmalonic aciduria, as well as hyper IgD and periodic fever syndrome (HIDS). (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：359 / 364

页数：6

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