Cleavage of sterol regulatory element binding proteins (SREBPs) by CPP32 during apoptosis - PubMed (original) (raw)
. 1996 Mar 1;15(5):1012-20.
Affiliations
- PMID: 8605870
- PMCID: PMC449996
Cleavage of sterol regulatory element binding proteins (SREBPs) by CPP32 during apoptosis
X Wang et al. EMBO J. 1996.
Abstract
Cellular cholesterol homeostasis is controlled by sterol-regulated proteolysis of membrane-bound transcription factors called sterol-regulatory element binding proteins (SREBPs). CPP32, a cysteine protease, was shown previously to cleave SREBP-1 and SREBP-2 in vitro at an aspartic acid between the basic helix-loop-helix leucine zipper domain and the first trans-membrane domain, liberating a transcriptionally active fragment. Here, we show that CPP32 exists in an inactive 32 kDa form in Chinese hamster ovary (CHO) cells. When apoptosis was induced with the protein kinase inhibitor staurosporine, CPP32 was cleaved to subunits of 20 and 10 kDa to form the active protease. Under these conditions membrane-bound SREBP-1 and SREBP-2 were both cleaved, and the transcriptionally active N-terminal fragments were found in nuclear extracts. Similar results were obtained in human U937 cells induced to undergo apoptosis by anti-Fas and etoposide. The apoptosis-induced cleavage of SREBPs was not suppressed by sterols, indicating that apoptosis-induced cleavage and sterol-regulated cleavage are mediated by different proteases. CHO cells expressing a mutant SREBP-2 with an Asp--> Ala mutation at the CPP32 cleavage site showed sterol-regulated cleavage but no apoptosis-induced cleavage. These data are consistent with the emerging concept that CPP32 is a central mediator in apoptosis. They also indicate that SREBPs, like poly (ADP) ribose polymerase, are cleaved by CPP32 during programmed cell death.
Similar articles
- Purification of an interleukin-1 beta converting enzyme-related cysteine protease that cleaves sterol regulatory element-binding proteins between the leucine zipper and transmembrane domains.
Wang X, Pai JT, Wiedenfeld EA, Medina JC, Slaughter CA, Goldstein JL, Brown MS. Wang X, et al. J Biol Chem. 1995 Jul 28;270(30):18044-50. doi: 10.1074/jbc.270.30.18044. J Biol Chem. 1995. PMID: 7629113 - Purification and cDNA cloning of a second apoptosis-related cysteine protease that cleaves and activates sterol regulatory element binding proteins.
Pai JT, Brown MS, Goldstein JL. Pai JT, et al. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5437-42. doi: 10.1073/pnas.93.11.5437. Proc Natl Acad Sci U S A. 1996. PMID: 8643593 Free PMC article. - Regulated cleavage of sterol regulatory element binding proteins requires sequences on both sides of the endoplasmic reticulum membrane.
Hua X, Sakai J, Brown MS, Goldstein JL. Hua X, et al. J Biol Chem. 1996 Apr 26;271(17):10379-84. doi: 10.1074/jbc.271.17.10379. J Biol Chem. 1996. PMID: 8626610 - Maintaining cholesterol homeostasis: sterol regulatory element-binding proteins.
Weber LW, Boll M, Stampfl A. Weber LW, et al. World J Gastroenterol. 2004 Nov 1;10(21):3081-7. doi: 10.3748/wjg.v10.i21.3081. World J Gastroenterol. 2004. PMID: 15457548 Free PMC article. Review. - Sterol regulatory element-binding protein family as global regulators of lipid synthetic genes in energy metabolism.
Shimano H. Shimano H. Vitam Horm. 2002;65:167-94. doi: 10.1016/s0083-6729(02)65064-2. Vitam Horm. 2002. PMID: 12481547 Review.
Cited by
- Metabolic Injury of Hepatocytes Promotes Progression of NAFLD and AALD.
Carvalho-Gontijo R, Han C, Zhang L, Zhang V, Hosseini M, Mekeel K, Schnabl B, Loomba R, Karin M, Brenner DA, Kisseleva T. Carvalho-Gontijo R, et al. Semin Liver Dis. 2022 Aug;42(3):233-249. doi: 10.1055/s-0042-1755316. Epub 2022 Aug 24. Semin Liver Dis. 2022. PMID: 36001995 Free PMC article. Review. - β2-spectrin (SPTBN1) as a therapeutic target for diet-induced liver disease and preventing cancer development.
Rao S, Yang X, Ohshiro K, Zaidi S, Wang Z, Shetty K, Xiang X, Hassan MI, Mohammad T, Latham PS, Nguyen BN, Wong L, Yu H, Al-Abed Y, Mishra B, Vacca M, Guenigault G, Allison MED, Vidal-Puig A, Benhammou JN, Alvarez M, Pajukanta P, Pisegna JR, Mishra L. Rao S, et al. Sci Transl Med. 2021 Dec 15;13(624):eabk2267. doi: 10.1126/scitranslmed.abk2267. Epub 2021 Dec 15. Sci Transl Med. 2021. PMID: 34910547 Free PMC article. - Scap structures highlight key role for rotation of intertwined luminal loops in cholesterol sensing.
Kober DL, Radhakrishnan A, Goldstein JL, Brown MS, Clark LD, Bai XC, Rosenbaum DM. Kober DL, et al. Cell. 2021 Jul 8;184(14):3689-3701.e22. doi: 10.1016/j.cell.2021.05.019. Epub 2021 Jun 16. Cell. 2021. PMID: 34139175 Free PMC article. - DNA damage promotes ER stress resistance through elevation of unsaturated phosphatidylcholine in Caenorhabditis elegans.
Deng J, Bai X, Tang H, Pang S. Deng J, et al. J Biol Chem. 2021 Jan-Jun;296:100095. doi: 10.1074/jbc.RA120.016083. Epub 2020 Nov 24. J Biol Chem. 2021. PMID: 33208465 Free PMC article. - Efferocytosis potentiates the expression of arachidonate 15-lipoxygenase (ALOX15) in alternatively activated human macrophages through LXR activation.
Snodgrass RG, Benatzy Y, Schmid T, Namgaladze D, Mainka M, Schebb NH, Lütjohann D, Brüne B. Snodgrass RG, et al. Cell Death Differ. 2021 Apr;28(4):1301-1316. doi: 10.1038/s41418-020-00652-4. Epub 2020 Nov 11. Cell Death Differ. 2021. PMID: 33177619 Free PMC article.
References
- Trends Pharmacol Sci. 1989 Jun;10(6):218-20 - PubMed
- J Biol Chem. 1995 May 19;270(20):12152-61 - PubMed
- Dev Biol. 1990 Mar;138(1):33-41 - PubMed
- Nature. 1992 Apr 2;356(6368):397-400 - PubMed
- Science. 1993 Mar 19;259(5102):1769-71 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous