Sterol-regulated release of SREBP-2 from cell membranes requires two sequential cleavages, one within a transmembrane segment.

Abstract:

:Sterol regulatory element binding proteins (SREBPs) are transcription factors attached to the endoplasmic reticulum. The NH2-segment, which activates transcription, is connected to membranes by a hairpin anchor formed by two transmembrane sequences and a short lumenal loop. Using H-Ras-SREBP-2 fusion proteins, we show that the NH2-segment is released from membranes by two sequential cleavages. The first, regulated by sterols, occurs in the lumenal loop. The second, not regulated by sterols, occurs within the first transmembrane domain. The liberated NH2-segment enters the nucleus and activates genes controlling cholesterol synthesis and uptake. Certain mutant Chinese hamster ovary cells are auxotrophic for cholesterol because they fail to carry out the second cleavage; the NH2-segment remains membrane-bound and transcription is not activated.

journal_name

Cell

journal_title

Cell

authors

Sakai J,Duncan EA,Rawson RB,Hua X,Brown MS,Goldstein JL

doi

10.1016/s0092-8674(00)81304-5

subject

Has Abstract

pub_date

1996-06-28 00:00:00

pages

1037-46

issue

7

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(00)81304-5

journal_volume

85

pub_type

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