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: Szabolcs Bellyei, Andras Szigeti, Eva Pozsgai, Arpad Boronkai, Eva Gomori, Eniko Hocsak, Robert Farkas, Balazs Sumegi, Ferenc Gallyas Jr
• Journal: European journal of cell biology (Eur J Cell Biol) Vol. 86 Issue 3 Pg. 161-71 (Mar 2007) ISSN: 0171-9335 [Print] Germany
• PMID: 17275951 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HSPB11 protein, human
• Heat-Shock Proteins, Small
• Intracellular Signaling Peptides and Proteins
• Etoposide
• Cytochromes c
• Caspase 3

Topics

• Amino Acid Sequence
• Animals
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cytochromes c (metabolism)
• Enzyme Activation (drug effects)
• Etoposide (pharmacology)
• Gene Expression (drug effects)
• Genome, Human (drug effects, genetics)
• HeLa Cells
• Heat-Shock Proteins, Small (chemistry, metabolism)
• Humans
• Intracellular Signaling Peptides and Proteins
• Mice
• Molecular Sequence Data
• NIH 3T3 Cells
• Protein Processing, Post-Translational (drug effects)
• Protein Structure, Quaternary (drug effects)
• Protein Transport (drug effects)
• Sequence Alignment
• Sequence Homology
• Temperature