Identification of Regulatory and Catalytic Domains in the Apoptosis Nuclease DFF40/CAD
Copyright policy )Identification of Regulatory and Catalytic Domains in the Apoptosis Nuclease DFF40/CAD
The DNA fragmentation factor (DFF) is composed of two subunits, the 40-kDa caspase-3-activated nuclease (DFF40/CAD) and its 45-kDa inhibitor (DFF45/ICAD). During apoptosis, DFF-40/CAD is activated by caspase-3-mediated cleavage of DFF45/ICAD. Mutational analysis of DFF40/CAD revealed that DFF40/CAD is composed of a C-terminal catalytic domain and an N-terminal regulatory domain. Deletion of the catalytic domain (residues 290-345) abrogated the caspase-3-induced nuclease activity of DFF40/CAD but not its ability to interact with DFF45/ICAD. Conversely, removal of the regulatory domain (residues 1-83) yielded a constitutively active DFF40/CAD nuclease that neither bound to its inhibitor nor required caspase-3 for activation. Amino acid alignment revealed that the regulatory domain of DFF40/CAD has homology to the N-terminal region of mammalian and Drosophila DFF45/ICAD and CIDE-N, a regulatory domain previously identified in pro-apoptotic CIDE proteins. Mutational analysis of the N-terminal region revealed mutants with diminished nuclease activity but with intact ability to bind DFF45/ICAD. Thus, CIDE-N represents a new type of domain that is associated with the regulation of the apoptosis/DNA fragmentation pathway.
- University of Michigan–Flint United States
Deoxyribonucleases, Sequence Homology, Amino Acid, Caspase 3, Molecular Sequence Data, Intracellular Signaling Peptides and Proteins, Apoptosis, Enzyme Activation, Caspases, Catalytic Domain, Animals, Humans, Amino Acid Sequence, Apoptosis Regulatory Proteins, Poly-ADP-Ribose Binding Proteins
Deoxyribonucleases, Sequence Homology, Amino Acid, Caspase 3, Molecular Sequence Data, Intracellular Signaling Peptides and Proteins, Apoptosis, Enzyme Activation, Caspases, Catalytic Domain, Animals, Humans, Amino Acid Sequence, Apoptosis Regulatory Proteins, Poly-ADP-Ribose Binding Proteins
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