Jt. Pai et al., PURIFICATION AND CDNA CLONING OF A 2ND APOPTOSIS-RELATED CYSTEINE PROTEASE THAT CLEAVES AND ACTIVATES STEROL REGULATORY ELEMENT-BINDING PROTEINS, Proceedings of the National Academy of Sciences of the United Statesof America, 93(11), 1996, pp. 5437-5442
We have purified from hamster liver a second cysteine protease that cl
eaves and activates sterol regulatory element binding proteins (SREBPs
). cDNA cloning revealed that this enzyme is the hamster equivalent of
Mch3, a human enzyme that is related to the interleukin 1 beta conver
ting enzyme. We call this enzyme Mch3/SCA-2. It is 54% identical to ha
mster CPP32/SCA-1, a cysteine protease that was earlier shown to cleav
e SREBPs at a conserved Asp between the basic helix-loop-helix leucine
zipper domain and the membrane attachment domain. This cleavage liber
ates an NH2-terminal fragment of approximate to 460 amino acids that a
ctivates transcription of genes encoding the low density lipoprotein r
eceptor and enzymes of cholesterol synthesis. Mch3/SCA-2 and CPP32/SCA
-1 are synthesized as inactive 30-35 kDa precursors that are thought t
o be cleaved during apoptosis to generate active fragments of approxim
ate to 20 and approximate to 10 kDa. The current data lend further sup
port to the notion that SREBPs are cleaved and activated as part of th
e program in programmed cell death.