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
Celljournal_title
Cellauthors
Sakai J,Duncan EA,Rawson RB,Hua X,Brown MS,Goldstein JLdoi
10.1016/s0092-8674(00)81304-5subject
Has Abstractpub_date
1996-06-28 00:00:00pages
1037-46issue
7eissn
0092-8674issn
1097-4172pii
S0092-8674(00)81304-5journal_volume
85pub_type
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