Identification of the nuclear factor HMG2 as an activator for DFF nuclease activity.
DNA fragmentation during apoptosis is mediated by a heterodimeric protein complex, DFF45/ICAD and DFF40/CAD/CPAN. Purified DFF40 alone possesses intrinsic nuclease activity that is inhibited by its association with DFF45. The proteolytic cleavage of DFF45 by caspase-3 frees the DFF40 subunit to function as a nuclease. In the course of identifying factors that stimulate DFF activity, we have isolated a nuclear factor and identified it as the high mobility group protein 2 (HMG2). We found that bacterially expressed HMG2 is able to enhance the nuclease activity of DFF. As HMG2 has DNA bending activity (6), our data suggest that HMG proteins may augment DNA fragmentation during apoptosis through changes in chromosome structure.
Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore, 117609, Singapore.
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D000595:Amino Acid Sequence; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D053938:DNA Fragmentation; D004789:Enzyme Activation; D006367:HeLa Cells; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D006609:High Mobility Group Proteins; D011506:Proteins; D011994:Recombinant Proteins; C109664:caspase-activated DNase inhibitor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases