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Sci. STKE, 26 September 2000
Vol. 2000, Issue 51, p. tw4
[DOI: 10.1126/stke.2000.51.tw4]

EDITORS' CHOICE

Sterol Regulation Sterols Promote Retention

Lipid biosynthesis and uptake is regulated by the intracellular sterol level, indirectly by sterol-regulatory element binding proteins (SREBPs), which control the synthesis of lipogenic genes. The intracellular sterol level is sensed by SREBP cleavage-activating proteins (SCAPs) in the endoplasmic reticulum (ER), which then control the movement and subsequent activation of the SREBP transcription factors. The transcription factors arise from cleavage of SREBPs after transport to the Golgi. SCAP and SREBP form a complex that moves from the ER to the Golgi, and SCAPs have a sterol-sensing domain that allows increased intracellular sterols to block this ER-to-Golgi transport of the SCAP/SREBP complex. Yang et al. transfected cells with cDNAs encoding the sterol-sensing domain of SCAP or encoding a SCAP unable to interact with SREBPs. These SCAP fragments promoted Golgi delivery and blocked the suppression of SREBP cleavage and nuclear accumulation of active SREBP in response to increasing sterol concentration. When the sterol-sensing domain of the SCAP fragments was mutated, then this inhibition did not occur. These data suggest that the SCAP fragments compete for binding to a retention molecule in the presence of increased sterols. This supports a model whereby SCAP/SREBP is constitutively transported to the Golgi and increased sterols promote ER retention of the complex.

Yang, T., Goldstein, J.L., and Brown, M.S. (2000) Overexpression of membrane domain of SCAP prevent sterols from inhibiting SCAP-SREBP exit from endoplasmic reticulum. J. Biol. Chem. 275: 29881-29886. [Abstract] [Full Text]

Citation: Sterols Promote Retention. Sci. STKE 2000, tw4 (2000).


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