Selective cleavage of nuclear autoantigens during CD95 (Fas/APO-1)-mediated T cell apoptosis - PubMed (original) (raw)
Selective cleavage of nuclear autoantigens during CD95 (Fas/APO-1)-mediated T cell apoptosis
C A Casiano et al. J Exp Med. 1996.
Abstract
Intracellular proteases appear to be important mediators of apoptosis. Substrates cleaved by proteases during apoptosis include nuclear autoantigens targeted in systemic autoimmune diseases. Using human autoantibodies as probes, we demonstrate here that T cell apoptosis mediated by CD95 (Fas/APO-1) is associated with substantial cleavage of a subset of nuclear autoantigens (7 of 33 examined). This subset included poly (ADP-ribose) polymerase, the 70-kD protein of the U1 small nuclear ribonucleoprotein particle, lamin B, the nuclear mitotic apparatus protein NuMA, DNA topoisomerases I and II, and the RNA polymerase I upstream binding factor UBF. Several of the cleaved autoantigens are involved in ensuring the integrity and proper conformation of DNA in the nucleus through interactions with the nuclear matrix, suggesting the possibility that their cleavage may contribute to the collapse of nuclear structure during apoptosis. The relative cleavage kinetics indicated that the autoantigens were targeted at various times after induction of apoptosis, suggesting either differential accessibility or activation of distinct proteases during the cell death process. These data reinforce the hypothesis that apoptosis is accompanied by selective cleavage of key substrates and not by a generalized degradation of intracellular material.
Similar articles
- Bcl-2 prevents CD95 (Fas/APO-1)-induced degradation of lamin B and poly(ADP-ribose) polymerase and restores the NF-kappaB signaling pathway.
Mandal M, Maggirwar SB, Sharma N, Kaufmann SH, Sun SC, Kumar R. Mandal M, et al. J Biol Chem. 1996 Nov 29;271(48):30354-9. doi: 10.1074/jbc.271.48.30354. J Biol Chem. 1996. PMID: 8939996 - NuMA and nuclear lamins behave differently in Fas-mediated apoptosis.
Taimen P, Kallajoki M. Taimen P, et al. J Cell Sci. 2003 Feb 1;116(Pt 3):571-83. doi: 10.1242/jcs.00227. J Cell Sci. 2003. PMID: 12508117 - Secondary necrosis is a source of proteolytically modified forms of specific intracellular autoantigens: implications for systemic autoimmunity.
Wu X, Molinaro C, Johnson N, Casiano CA. Wu X, et al. Arthritis Rheum. 2001 Nov;44(11):2642-52. doi: 10.1002/1529-0131(200111)44:11<2642::aid-art444>3.0.co;2-8. Arthritis Rheum. 2001. PMID: 11710720 - Antinuclear autoantibodies: probes for defining proteolytic events associated with apoptosis.
Casiano CA, Tan EM. Casiano CA, et al. Mol Biol Rep. 1996;23(3-4):211-6. doi: 10.1007/BF00351171. Mol Biol Rep. 1996. PMID: 9112231 Review. - Cleavage of poly(ADP-ribose) polymerase: a sensitive parameter to study cell death.
Duriez PJ, Shah GM. Duriez PJ, et al. Biochem Cell Biol. 1997;75(4):337-49. Biochem Cell Biol. 1997. PMID: 9493956 Review.
Cited by
- Molecular Mechanisms Linking Inflammation to Autoimmunity in Sjögren's Syndrome: Identification of New Targets.
Sisto M, Ribatti D, Lisi S. Sisto M, et al. Int J Mol Sci. 2022 Oct 30;23(21):13229. doi: 10.3390/ijms232113229. Int J Mol Sci. 2022. PMID: 36362017 Free PMC article. Review. - Differential molecular response in mice and human thymocytes exposed to a combined-dose radiation regime.
López-Nieva P, González-Vasconcellos I, González-Sánchez L, Cobos-Fernández MA, Ruiz-García S, Sánchez Pérez R, Aroca Á, Fernández-Piqueras J, Santos J. López-Nieva P, et al. Sci Rep. 2022 Feb 24;12(1):3144. doi: 10.1038/s41598-022-07166-8. Sci Rep. 2022. PMID: 35210498 Free PMC article. - Docosahexaenoic acid protection against palmitic acid-induced lipotoxicity in NGF-differentiated PC12 cells involves enhancement of autophagy and inhibition of apoptosis and necroptosis.
Montero ML, Liu JW, Orozco J, Casiano CA, De Leon M. Montero ML, et al. J Neurochem. 2020 Dec;155(5):559-576. doi: 10.1111/jnc.15038. Epub 2020 Jun 8. J Neurochem. 2020. PMID: 32379343 Free PMC article. - Altered Traffic of Cardiolipin during Apoptosis: Exposure on the Cell Surface as a Trigger for "Antiphospholipid Antibodies".
Manganelli V, Capozzi A, Recalchi S, Signore M, Mattei V, Garofalo T, Misasi R, Degli Esposti M, Sorice M. Manganelli V, et al. J Immunol Res. 2015;2015:847985. doi: 10.1155/2015/847985. Epub 2015 Sep 29. J Immunol Res. 2015. PMID: 26491702 Free PMC article. Review. - The Wnt Target Protein Peter Pan Defines a Novel p53-independent Nucleolar Stress-Response Pathway.
Pfister AS, Keil M, Kühl M. Pfister AS, et al. J Biol Chem. 2015 Apr 24;290(17):10905-18. doi: 10.1074/jbc.M114.634246. Epub 2015 Mar 10. J Biol Chem. 2015. PMID: 25759387 Free PMC article.
References
- Nature. 1989 Jun 22;339(6226):625-6 - PubMed
- J Cell Sci. 1996 Feb;109 ( Pt 2):277-88 - PubMed
- J Exp Med. 1994 Apr 1;179(4):1317-30 - PubMed
- J Cell Biol. 1994 Aug;126(4):827-37 - PubMed
- Mol Cell Biol. 1994 Sep;14(9):6297-305 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous