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Vol. 9, Issue 12, 3445-3453, December 1998

Degradation of Stearoyl-Coenzyme A Desaturase: Endoproteolytic Cleavage by an Integral Membrane Protease

F. Scott Heinemann,* and Juris Ozolsdagger Dagger

 *Department of Pathology, Hoag Memorial Hospital Presbyterian, Newport Beach, California 92663; and  dagger Department of Biochemistry, University of Connecticut Health Center, Farmington, Connecticut 06030-3305

Stearoyl-coenzyme A desaturase (SCD) is a key regulator of membrane fluidity, turns over rapidly, and represents a prototype for selective degradation of resident proteins of the endoplasmic reticulum. Using detergent-solubilized, desaturase-induced rat liver microsomes we have characterized a protease that degrades SCD. Degradation of SCD in vitro is highly selective, has a half-life of 3-4 h, and generates a 20-kDa C-terminal fragment of SCD. The N terminus of the 20-kDa fragment was identified as Phe177. The cleavage site occurs in a conserved 12-residue hydrophobic segment of SCD flanked by clusters of basic residues. The SCD protease remains associated with microsomal membranes after peripheral and lumenal proteins have been selectively removed. SCD protease is present in normal rat liver microsomes and cleaves purified SCD. We conclude that rapid turnover of SCD involves a constitutive microsomal protease with properties of an integral membrane protein.


Dagger    Corresponding author.


Molecular Biology of the Cell
Vol. 9, 3445-3453, December 1998
Copyright © 1998 by The American Society for Cell Biology



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