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
StatePublished - May 28 1996

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Sterol Regulatory Element Binding Proteins
Cysteine Proteases
Organism Cloning
Complementary DNA
Cricetinae
Apoptosis
Enzymes
Leucine Zippers
Caspase 1
LDL Receptors
Viperidae
Cell Death
Cholesterol
Amino Acids
Membranes
Liver
Genes

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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title = "Purification and cDNA cloning of a second apoptosis-related cysteine protease that cleaves and activates sterol regulatory element binding proteins",
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.",
keywords = "cholesterol, CPP32 protease, Mch3 protease, poly(ADP-ribose) polymerase, programmed cell death",
author = "Pai, {Jih Tung} and Brown, {Michael S.} and Goldstein, {Joseph L.}",
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AU - Pai, Jih Tung

AU - Brown, Michael S.

AU - Goldstein, Joseph L.

PY - 1996/5/28

Y1 - 1996/5/28

N2 - 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.

AB - 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.

KW - cholesterol

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KW - poly(ADP-ribose) polymerase

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