Wang X, Sato R, Brown M S, Hua X, Goldstein J L
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Cell. 1994 Apr 8;77(1):53-62. doi: 10.1016/0092-8674(94)90234-8.
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.
固醇调节元件结合蛋白1（SREBP-1）是转录因子碱性螺旋-环-螺旋-亮氨酸拉链（bHLH-ZIP）家族的成员，它以125kd的前体形式合成，该前体附着于核膜和内质网。在固醇缺乏的细胞中，膜结合前体被切割以产生可溶性的NH2末端片段（表观分子量为68kd），该片段易位至细胞核。这个包含bHLH-ZIP结构域的片段可激活低密度脂蛋白（LDL）受体和HMG CoA合酶基因的转录。固醇抑制SREBP-1的切割，并且68kd的核形式会迅速被分解代谢，从而减少转录。ALLN（一种中性半胱氨酸蛋白酶抑制剂）可阻断68kd形式的分解，并超诱导固醇调节基因。膜结合转录因子的固醇调节蛋白水解提供了一种新机制，通过该机制转录可由膜脂调节。
