SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis

X Wang, R Sato, MS Brown, X Hua, JL Goldstein - Cell, 1994 - cell.com
X Wang, R Sato, MS Brown, X Hua, JL Goldstein
Cell, 1994cell.com
Sterol regulatory element-bindlng proteln 1 (SREBP-l), a member of the basic-helix-loop-
helix-leucine zipper (LHLH-ZIP) family of transcription factors, Is synthesized as a 125 kd
precursor that Is attached to the nuclear envelope and endoplasmic reticulum. In sterol-
depleted cells, the membrane-bound precursor is cleaved to genemte a soluble NHitermlnal
fmgment (apparent molecular mas8, 66 kd) that tmnslocates to the nucleus. This fragment,
which includes the bHLH-ZIP domain, activates transcription of the genes for the LDL …
Summary
Sterol regulatory element-bindlng proteln 1 (SREBP-l), a member of the basic-helix-loop-helix-leucine zipper (LHLH-ZIP) family of transcription factors, Is synthesized as a 125 kd precursor that Is attached to the nuclear envelope and endoplasmic reticulum. In sterol-depleted cells, the membrane-bound precursor is cleaved to genemte a soluble NHitermlnal fmgment (apparent molecular mas8, 66 kd) that tmnslocates to the nucleus. This fragment, which includes the bHLH-ZIP domain, activates transcription of the genes for the LDL receptor and HMO CoA synthase. Sterols lnhlblt the cleavage of SREBP-1, and the 66 kd nuclear form is mpldly catabolized, thereby reducing transcrlptlon. ALLN, an inhibitor of neutml cysteine pro% ases, block8 the breakdown of the 66 kd form and superinduces sterol-regulated genes. Sterol-regulated pmteolysls of a membrane-bound tmnscriptkm factor provktes a novel mechanism by which transcription can be regulated by membrane lipids.
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