Degradation of stearoyl coenzyme A desaturase: Endoproteolytic cleavage byan integral membrane protease

Stearoyl-coenzyme A desaturase (SCD) is a key regulator of membrane fluidit y, turns over rapidly, and represents a prototype for selective degradation of resident proteins of the endoplasmic reticulum. Using detergent-solubil ized, desaturase-induced rat liver microsomes we have characterized a prote ase 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. T he N terminus of the 20-kDa fragment was identified as Phe(177). The cleava ge site occurs in a conserved 12-residue hydrophobic segment of SCD flanked by clusters of basic residues. The SCD protease remains associated with mi crosomal membranes after peripheral and lumenal proteins have been selectiv ely removed. SCD protease is present in normal rat liver microsomes and cle aves purified SCD. We conclude that rapid turnover of SCD involves a consti tutive microsomal protease with properties of an integral membrane protein.