Modulation of heat-shock protein 27 (Hsp27) anti-apoptotic activity by methylglyoxal modification.
Methylglyoxal (MG) is one of the side-products in glycolysis, and it reacts with proteins under physiological conditions. Here, we identified heat-shock protein 27 (Hsp27) as a major MG-modified protein in cells. MG modification of Hsp27 selectively occurs at Arg-188 to form argpyrimidine, and mutation in the residue represses the formation of a large oligomer. This modification process is essential to its repressing activity for cytochrome c-mediated caspase activation. Inhibition of MG modification of Hsp27 causes sensitization of the cells to anti-tumor drug-induced apoptosis. Thus, MG is a novel modulator of cell survival by directly incorporating with the specific protein residue.
Sakamoto
Hiroshi
H
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, 170-8455, Japan.
Mashima
Tetsuo
T
Yamamoto
Kazuo
K
Tsuruo
Takashi
T
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology*; D002850:Chromatography, Gel; D003574:Cytochrome c Group / Q000378:metabolism; D004789:Enzyme Activation; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011765:Pyruvaldehyde / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D003574:Cytochrome c Group; D006360:Heat-Shock Proteins; D011765:Pyruvaldehyde; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases