Purification and cDNA cloning of a second apoptosis-related cysteine protease that cleaves and activates sterol regulatory element binding proteins.
We have purified from hamster liver a second cysteine protease that cleaves 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 1beta converting enzyme. We call this enzyme Mch3/SCA-2. It is 54% identical to hamster CPP32/SCA-1, a cysteine protease that was earlier shown to cleave SREBPs at a conserved Asp between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. This cleavage liberates an NH2-terminal fragment of approximately 460 amino acids that activates transcription of genes encoding the low density lipoprotein receptor and enzymes of cholesterol synthesis. Mch3/SCA-2 and CPP32/SCA-I are synthesized as inactive 30-35 kDa precursors that are thought to be cleaved during apoptosis to generate active fragments of approximately 20 and approximately 10 kDa. The current data lend further support to the notion that SREBPs are cleaved and activated as part of the program in programmed cell death.
Pai
J T
JT
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, 75235-9046, USA.
Brown
M S
MS
Goldstein
J L
JL
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001224:Aspartic Acid; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D053148:Caspase 3; D020169:Caspases; D002845:Chromatography; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D003001:Cloning, Molecular; D017124:Conserved Sequence; D006224:Cricetinae; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D016350:Leucine Zippers; D008099:Liver / Q000201:enzymology*; D008297:Male; D008647:Mesocricetus; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D017386:Sequence Homology, Amino Acid; D051780:Sterol Regulatory Element Binding Protein 1; D013379:Substrate Specificity; D014157:Transcription Factors
D022762:CCAAT-Enhancer-Binding Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D001224:Aspartic Acid; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases