Functional Interaction of DFF35 and DFF45 with Caspase-activated DNA Fragmentation Nuclease DFF40

DNA fragmentation factor (DFF) functions downstream of caspase-3 and directly triggers DNA fragmentation during apoptosis. Here we described the identification and characterization of DFF35, an isoform of DFF45 comprised of 268 amino acids. Functional assays have shown that only DFF45, not DFF35, ca...

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Bibliographic Details
Published in:The Journal of biological chemistry 1999-07, Vol.274 (30), p.20759-20762
Main Authors: Gu, Jijie, Dong, Rui-Ping, Zhang, Chonghui, McLaughlin, Daniel F., Wu, Mei X., Schlossman, Stuart F.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Apoptosis
Apoptosis Regulatory Proteins
Binding Sites
Deoxyribonucleases - genetics
Deoxyribonucleases - metabolism
DNA Fragmentation
Humans
Intracellular Signaling Peptides and Proteins
Molecular Sequence Data
Poly-ADP-Ribose Binding Proteins
Protein Conformation
Protein Isoforms - genetics
Protein Isoforms - metabolism
Proteins - chemistry
Proteins - genetics
Proteins - metabolism
Sequence Alignment
Substrate Specificity
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Summary:DNA fragmentation factor (DFF) functions downstream of caspase-3 and directly triggers DNA fragmentation during apoptosis. Here we described the identification and characterization of DFF35, an isoform of DFF45 comprised of 268 amino acids. Functional assays have shown that only DFF45, not DFF35, can assist in the synthesis of highly active DFF40. Using the deletion mutants, we mapped the function domains of DFF35/45 and demonstrated that the intact structure/conformation of DFF45 is essential for it to function as a chaperone and assist in the synthesis of active DFF40. Whereas the amino acid residues 101–180 of DFF35/45 mediate its binding to DFF40, the amino acid residues 23–100, which is homologous between DFF35/45 and DFF40, may function to inhibit the activity of DFF40. In contrast to DFF45, DFF35 cannot work as a chaperone, but it can bind to DFF40 more strongly than DFF45 and can inhibit its nuclease activity. These findings suggest that DFF35 may function in vivo as an important alternative mechanism to inhibit the activity of DFF40 and further, that the inhibitory effects of both DFF35 and DFF45 on DFF40 can put the death machinery under strict control.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.274.30.20759