Purification and cDNA cloning of a second apoptosis-related cysteine protease that cleaves and activates sterol regulatory element binding proteins

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Abstract

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 1β 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 ≃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-1 are synthesized as inactive 30-35 kDa precursors that are thought to be cleaved during apoptosis to generate active fragments of ≃20 and ≃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.

Original languageEnglish (US)
Pages (from-to)5437-5442
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number11
DOIs
Publication statusPublished - May 28 1996

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Keywords

  • cholesterol
  • CPP32 protease
  • Mch3 protease
  • poly(ADP-ribose) polymerase
  • programmed cell death

ASJC Scopus subject areas

  • Genetics
  • General

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