Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2002-8-15
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1350-9047
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
915-25
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12181742-Apoptosis, pubmed-meshheading:12181742-Asthma, pubmed-meshheading:12181742-Autoimmune Diseases, pubmed-meshheading:12181742-Binding Sites, pubmed-meshheading:12181742-Caspase 3, pubmed-meshheading:12181742-Caspase 7, pubmed-meshheading:12181742-Caspases, pubmed-meshheading:12181742-Cell Survival, pubmed-meshheading:12181742-Culture Media, Serum-Free, pubmed-meshheading:12181742-Dermatitis, Atopic, pubmed-meshheading:12181742-Gene Expression Regulation, pubmed-meshheading:12181742-HeLa Cells, pubmed-meshheading:12181742-Humans, pubmed-meshheading:12181742-Hypersensitivity, Immediate, pubmed-meshheading:12181742-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:12181742-Jurkat Cells, pubmed-meshheading:12181742-Molecular Sequence Data, pubmed-meshheading:12181742-Mutation, pubmed-meshheading:12181742-Peptide Fragments, pubmed-meshheading:12181742-Peptide Hydrolases, pubmed-meshheading:12181742-Rhinitis, pubmed-meshheading:12181742-Sequence Homology, Amino Acid, pubmed-meshheading:12181742-Sequence Homology, Nucleic Acid
pubmed:year
2002
pubmed:articleTitle
Caspase cleavage of the nuclear autoantigen LEDGF/p75 abrogates its pro-survival function: implications for autoimmunity in atopic disorders.
pubmed:affiliation
Department of Biochemistry and Microbiology, Center for Molecular Biology and Gene Therapy, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't