Sterol regulatory element

Also, phosphorylation of Akt results in activation of sterol regulatory-element binding protein 1 (SREBP1), a key transcription factor involved in regulation of lipogenic enzymes. In addition, some of the effects of insulin on cell proliferation and survival may be explained by an Akt-dependent inhibition of apoptosis through phosphorylation and inactivation of proa-poptotic proteins (e.g., BAD, Caspase 9). 

Osborne TF. Sterol regulatory element binding protein (SREBPs) Key regulators of nutritional homeostasis and insulin action. J Biol Chem 2000 275 32379-32382. 

Muller PJ, Miserez AR. Mutations in the gene encoding sterol-regulatory element-binding protein-2 in hypercholes-terolaemic subjects. Atherosclerosis Supplements 2001 2 69. 

SREBP sterol regulatory element binding protein... 

Zhou, J., Zhai, Y., Mu, Y Gong, H., Uppal, H., Toma, D., Ren, S., Evans, R.M. and Xie, W. (2006) A novel pregnane X receptor-mediated and sterol regulatory element-hinding protein-independent lipogenic pathway. Journal of Biological Chemistry, 281, 15013—15020. 

FIGURE 21-43 SREBP activation. Sterol regulatory element-binding proteins (SREBPs, shown in green) are embedded in the ER when first synthesized, in a complex with the protein SREBP cleavage-activating protein (SCAP, red). (N and C represent the amino and carboxyl termini of the proteins.) When bound to SCAP, SREBPs are inactive. When... 

Includes a timely new discussion on the regulation of cholesterol metabolism at the genetic level, with consideration of sterol regulatory element-binding proteins (SREBPs). 

Regulation of HMG CoA reductase. SRE = sterol regulatory element SREBP = sterol regulatory elementbinding protein. 

Miserez AR, Muller PY, Barella L, Schwietert M, Erb P, Vemazza PL, Battegay M Swiss HIV Cohort Study. A single-nucleotide polymorphism in the sterol-regulatory element-binding protein lc gene is predictive of HTV-related hyperlipoproteinaemia. AIDS 2001 15 2045-9. 

Diomede L, Albani D, Bianchi M, Salmona M. Endotoxin regulates the maturation of sterol regulatory element binding protein-1 through the induction of cytokines. Eur Cytokine Netw 2001 12 625-630. 

Moon, Y. A., Shah, N. A., Mohapatra, S., Warrington, J. A. and Horton, J.D. (2001). Identification of a mammalian long chain fatty acyl elongase regulated by sterol regulatory element-binding proteins. J. Biol. Chem., 276,45358—45366. 

Shimano, H. 2001. Sterol regulatory element-binding proteins (SREBPs) transcriptional regulators of lipid synthetic genes. Prog. Lipid Res. 40, 439-452. 

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. 

The promoter region of the LDL receptor gene contains several regulatory elements that control its expression. One in particular, sterol regulatory element 1, is the binding site for SREBP. Under baseline conditions, SREBP are inactive proteins bound to the endoplasmic... 

Cholesteryl esters that are internalized via the LDL receptor are hydrolyzed to produce cholesterol and an acyl chain. Cholesterol, in (urn, activates the enzyme acyl-CoA cholesterol acyl-transferase (ACAT) which re-esterifies cholesterol. In an apparently futile cycle, the cholesteryl esters are hydrolyzed by cholesteryl ester hydrolase. The cholesterol moiety has several fates it may leave the cell and bind to an acceptor such as high-density lipoprotein (HDL), it may be converted to steroid hormones, or it may be reesterified by ACAT. When the cellular cholesterol concentration falls, the activity of HMG-CoA reductase is increased, as is the number of LDL receptors, which results in an increase of cellular cholesterol, due both to de novo synthesis and to the uptake of cholesterol-rich lipoproteins in the circulation. An increase in cellular cholesterol results in the rapid decline in the mRNA levels for both HMG-CoA reductase and the LDL receptor. This coordinated regulation is brought about by the presence of an eight nucleotide sequence on the genes which code for both proteins this is termed the sterol regulatory element-1. 

Horton, J. D., Shimomural I., Ikemoto, S., Bashmakov, Y., and Hammer, R. E. 2003. Overexpression of sterol regulatory element-binding protein-la in mouse adipose tissue produces adipocyte hypertrophy, increased fatty acid secretion, and fatty liver. J. Biol. Chem., 278, 36652-36660. 

Kim, H. J.,Takahashi, M., and Ezaki, 0.1999. Fish oil feeding decreases mature sterol regulatory element-binding protein 1 (SREBP-1) by down-regulation of SREBP-lc mRNA in mouse liver a possible mechanism for down-regulation of lipogenic enzyme mRNAs. J. Biol. Chem.,274, 25892-25898. 

Fatty acid synthase is transcriptionally regulated by upstream stimulatory factor and sterol regulatory element binding protein Ic (SREBP-lc), in response to feeding/insulin. 

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. 

The sterol regulatory-element-binding proteins (SREBPs)... 

E. A. Duncan, U. P. Dav, J. Sakai, J. L. Goldstein, and M. S. Brown. Second-site cleavage in sterol regulatory element binding protein occurs at transmembrane junenon as determined by cysteine panning. J Biol Chem, 273, 17801-17809, 1998. 

Kuhn, D. J., Bums, A. C., Kazi, A., Dou, Q. P. (2004). Direct inhibition of the ubiquitin-proteasome pathway by ester bond-containing green tea polyphenols is associated with increased expression of sterol regulatory element-binding protein 2 and LDL receptor. Biochim. Biophis. Acta, 1682, 1-10. 

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