Nuclear sterol regulatory element

Hirano, Y., Yoshida, M., Shimizu, M., and Sato, R. Direct demonstration of rapid degradation of nuclear sterol regulatory element-binding proteins by the ubiquitin-proteasome pathway. J Biol Chem 276 (2001) 36431-36437. 

Pai, J. T., Guryev, O., Brown, M. S., and Goldstein, J. L. Differential stimulation of cholesterol and unsaturated fatty acid biosynthesis in cells expressing individual nuclear sterol regulatory element-binding proteins. J Biol Chem 273 (1998) 26138-26148. 

Shimomura I, Shimano H, Korn BS, Bashmakov Y, Horton JD. 1998. Nuclear sterol regulatory element-binding proteins activate genes responsible for the entire program of unsaturated fatty acid biosynthesis in transgenic mouse liver. J Biol Chem 273 35299-35306. 

Members of a family of nuclear transcription factors called sterol regulatory element-binding proteins (SREBP) are responsible for the regulation of these cholesterol feedback mechanisms. SREBP are able to activate a number of genes encoding for proteins involved in the homeostasis of cholesterol and other lipids, including the LDL receptor gene itself. 

SREBPs are transcription factors that bind to the sterol regulatory element DNA sequence TCACNCCAC. Unactivated SREBPs are attached to the nuclear envelope and endoplasmic reticulum membranes. In cells with low levels of sterols, SREBPs are cleaved to a water-soluble N-terminal domain that is translocated to the nucleus. These activated SREBPs then bind to specific sterol regulatory element DNA sequences, thus up-regulating the synthesis of enzymes involved in sterol biosynthesis. Sterols in turn inhibit the cleavage of SREBPs and therefore synthesis of additional sterols is reduced through a negative-feedback loop. 

Briggs MR, Yokoyama C, Wang X, Brown MS, Goldstein JL (1993) Nuclear protein that binds sterol regulatory element of low density lipoprotein receptor promoter. I. Identification of the protein and delineation ofits target nucleotide sequence. J Biol Chem 268 14490-14496... 

Shimomura, I., Bashmakov, Y., Shimano, IT., ITorton, J.D., Goldstein, J.L. and Brown, M.S. Cholesterol feeding reduces nuclear forms of sterol regulatory element binding proteins in hamster liver. Proc Natl Acad Sci U S A, 94 (1997) 12354-12359. 

Inoue S, Yoshinari K, Sugawara M, Yamazoe Y (2011) Activated sterol regulatory element-binding protein-2 suppresses hepatocyte nuclear factor-4-mediated Cyp3all expression in mouse liver. Mol Pharmacol 79 148-156... 

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