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

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