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Caspase cleavage of the nuclear autoantigen LEDGF/p75 abrogates its pro-survival function: implications for autoimmunity in atopic disorders.
- Source :
-
Cell death and differentiation [Cell Death Differ] 2002 Sep; Vol. 9 (9), pp. 915-25. - Publication Year :
- 2002
-
Abstract
- Lens epithelium-derived growth factor p75 (LEDGF/p75) is a nuclear autoantigen in atopic disorders implicated in cellular protection against stress-induced apoptosis. We observed that LEDGF/p75 was cleaved during apoptosis into fragments of 65 and 58 kD generated by caspases-3 and -7 cleaving at three sites: DEVPD30/G, DAQD486/G and WEID85/N. Sequence analysis revealed that the DEVPD30/G and WEID85/N sites lie within the highly conserved HATH (homologous to amino terminus of hepatoma-derived growth factor) region, also known as PWWP domain. Alignment of proteins containing this domain failed to reveal conservation of the DEVPD30/G and WEID85/N sites, suggesting that the HATH/PWWP domain of LEDGF/p75 may be specifically targeted by caspases. Overexpression of LEDGF/p75 protected HepG2 cells from serum starvation-induced cell death, whereas expression of the 65 kD fragment failed to protect. The apoptotic cleavage of LEDGF/p75 may contribute to the pathogenesis of atopic disorders by abrogating its pro-survival function and enhancing its immunogenicity.
- Subjects :
- Apoptosis genetics
Asthma enzymology
Asthma genetics
Asthma immunology
Autoimmune Diseases enzymology
Autoimmune Diseases genetics
Binding Sites genetics
Caspase 3
Caspase 7
Caspases metabolism
Culture Media, Serum-Free pharmacology
Dermatitis, Atopic enzymology
Dermatitis, Atopic genetics
Dermatitis, Atopic immunology
Gene Expression Regulation genetics
HeLa Cells
Humans
Hypersensitivity, Immediate enzymology
Hypersensitivity, Immediate genetics
Intercellular Signaling Peptides and Proteins genetics
Intercellular Signaling Peptides and Proteins metabolism
Jurkat Cells
Molecular Sequence Data
Mutation physiology
Peptide Fragments genetics
Peptide Fragments immunology
Peptide Fragments metabolism
Peptide Hydrolases metabolism
Rhinitis enzymology
Rhinitis genetics
Rhinitis immunology
Sequence Homology, Amino Acid
Sequence Homology, Nucleic Acid
Apoptosis immunology
Autoimmune Diseases immunology
Caspases immunology
Cell Survival immunology
Hypersensitivity, Immediate immunology
Intercellular Signaling Peptides and Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1350-9047
- Volume :
- 9
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cell death and differentiation
- Publication Type :
- Academic Journal
- Accession number :
- 12181742
- Full Text :
- https://doi.org/10.1038/sj.cdd.4401063