title: Preventing apoptotic cell death by a novel small heat shock protein.
abstract: NCBI database analysis indicated that the human C1orf41 protein (small heat shock-like protein-Hsp16.2) has sequence similarity with small heat shock proteins (sHsps). Since sHsps have chaperone function, and so prevent aggregation of denatured proteins, we determined whether Hsp16.2 could prevent the heat-induced aggregation of denatured proteins. Under our experimental conditions, recombinant Hsp16.2 prevented aggregation of aldolase and glyceraldehyde-3-phosphate dehydrogenase, and protected Escherichia coli cells from heat stress indicating its chaperone function. Hsp16.2 also formed oligomeric complexes in aqueous solution. Hsp16.2 was found to be expressed at different levels in cell lines and tissues, and was mainly localized to the nucleus and the cytosol, but to a smaller extent, it could be also found in mitochondria. Hsp16.2 could be modified covalently by poly(ADP ribosylation) and acetylation. Hsp16.2 over-expression prevented etoposide-induced cell death as well as the release of mitochondrial cytochrome c and caspase activation. These data suggest that Hsp16.2 can prevent the destabilization of mitochondrial membrane systems and could represent a suitable target for modulating cell death pathways.
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pécs, 12 Szigeti Street, H-7624 Pécs, Hungary.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Bellyei
authors.forename: Andras
authors.initials: A
authors.lastname: Szigeti
authors.forename: Eva
authors.initials: E
authors.lastname: Pozsgai
authors.forename: Arpad
authors.initials: A
authors.lastname: Boronkai
authors.forename: Eva
authors.initials: E
authors.lastname: Gomori
authors.forename: Eniko
authors.initials: E
authors.lastname: Hocsak
authors.forename: Robert
authors.initials: R
authors.lastname: Farkas
authors.forename: Balazs
authors.initials: B
authors.lastname: Sumegi
authors.forename: Ferenc
authors.initials: F
authors.lastname: Gallyas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D015894:Genome, Human / Q000187:drug effects / Q000235:genetics; D006367:HeLa Cells; D050888:Heat-Shock Proteins, Small / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D020836:Protein Structure, Quaternary / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D016415:Sequence Alignment; D017385:Sequence Homology; D013696:Temperature
chemical_list: C525841:HSPB11 protein, human; D050888:Heat-Shock Proteins, Small; D047908:Intracellular Signaling Peptides and Proteins; D005047:Etoposide; D045304:Cytochromes c; D053148:Caspase 3