TY - JOUR
T1 - SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis
AU - Wang, Xiaodong
AU - Sato, Ryuichiro
AU - Brown, Michael S.
AU - Hua, Xianxin
AU - Goldstein, Joseph L.
N1 - Funding Information:
We thank Daphne Norsworthy and Garrett Lischer for excellent technical assistance; Barbara Gillis, Robin Craddock, and Edith Womack for invaluable help with tissue culture; our colleagues Scott Wooden and Jian Wu for helpful suggestions; and Dr. Alasdair MoDowall for help with confocal microscopy. This research is supported by grants from the National Institutes of Health (HL-20946) and the Perot Family Foundation. X. W. is the recipient of a postdoctoral fellowship from the Damon Runyon-Walter Winchell Cancer Research Fund (1156). R. S. was the recipient of a National Institutes of Health Fogarty International Research Fellowship (F05 TWD4571).
PY - 1994/4/8
Y1 - 1994/4/8
N2 - Sterol regulatory element-binding protein 1 (SREBP-1), a member of the basic-helix-loop-helix-leucine zipper (bHLH-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 generate a soluble NH2-terminal fragment (apparent molecular mass, 68 kd) that translocates to the nucleus. This fragment, which includes the bHLH-ZIP domain, activates transcription of the genes for the LDL receptor and HMG CoA synthase. Sterols inhibit the cleavage of SREBP-1, and the 68 kd nuclear form is rapidly catabolized, thereby reducing transcription. ALLN, an inhibitor of neutral cysteine proteases, blocks the breakdown of the 68 kd form and superinduces sterol-regulated genes. Sterol-regulated proteolysis of a membrane-bound transcription factor provides a novel mechanism by which transcription can be regulated by membrane lipids.
AB - Sterol regulatory element-binding protein 1 (SREBP-1), a member of the basic-helix-loop-helix-leucine zipper (bHLH-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 generate a soluble NH2-terminal fragment (apparent molecular mass, 68 kd) that translocates to the nucleus. This fragment, which includes the bHLH-ZIP domain, activates transcription of the genes for the LDL receptor and HMG CoA synthase. Sterols inhibit the cleavage of SREBP-1, and the 68 kd nuclear form is rapidly catabolized, thereby reducing transcription. ALLN, an inhibitor of neutral cysteine proteases, blocks the breakdown of the 68 kd form and superinduces sterol-regulated genes. Sterol-regulated proteolysis of a membrane-bound transcription factor provides a novel mechanism by which transcription can be regulated by membrane lipids.
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U2 - 10.1016/0092-8674(94)90234-8
DO - 10.1016/0092-8674(94)90234-8
M3 - Article
C2 - 8156598
AN - SCOPUS:0028225462
SN - 0092-8674
VL - 77
SP - 53
EP - 62
JO - Cell
JF - Cell
IS - 1
ER -