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Complementation Cloning of S2P, a Gene Encoding a Putative Metalloprotease Required for Intramembrane Cleavage of SREBPs
Ist Teil von
Molecular cell, 1997-12, Vol.1 (1), p.47-57
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
1997
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
We report the cloning of a gene,
S2P, that encodes a putative metalloprotease required for intramembrane proteolysis of sterol-regulatory element–binding proteins (SREBPs) at Site-2. SREBPs are membrane-bound transcription factors that activate genes regulating cholesterol metabolism. The active NH
2-terminal domains of SREBPs are released from membranes by sequential cleavage at two sites: Site-1, within the lumen of the endoplasmic reticulum; and Site-2, within a transmembrane segment. The human
S2P gene was cloned by complementation of mutant CHO cells that cannot cleave SREBPs at Site-2 and are cholesterol auxotrophs. S2P defines a new family of polytopic membrane proteins that contain an HE
XX H sequence characteristic of zinc metalloproteases. Mutation of the putative zinc-binding residues abolishes S2P activity.
S2P encodes an unusual metalloprotease that cleaves proteins within transmembrane segments.