PMID- 10318789
OWN - NLM
STAT- MEDLINE
DCOM- 19990617
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 20
DP  - 1999 May 14
TI  - Activation of the apoptotic endonuclease DFF40 (caspase-activated DNase or
      nuclease). Oligomerization and direct interaction with histone H1.
PG  - 13836-40
AB  - DNA fragmentation factor (DFF) is a heterodimeric protein composed of 45-kDa
      (DFF45) and 40-kDa (DFF40) subunits, a protein that mediates regulated DNA
      fragmentation and chromatin condensation in response to apoptotic signals. DFF45 
      is a specific molecular chaperone and an inhibitor for the nuclease activity of
      DFF40. Previous studies have shown that upon cleavage of DFF45 by caspase-3, the 
      nuclease activity of DFF40 is relieved of inhibition. Here we further investigate
      the mechanism of DFF40 activation. We demonstrate that DFF45 can also be cleaved 
      and inactivated by caspase-7 but not by caspase-6 and caspase-8. The cleaved
      DFF45 fragments dissociate from DFF40, allowing DFF40 to oligomerize to form a
      large functional complex that cleaves DNA by introducing double strand breaks.
      Histone H1 directly interacts with DFF, confers DNA binding ability to DFF, and
      stimulates the nuclease activity of DFF40 by increasing its Kcat and decreasing
      its Km.
FAU - Liu, X
AU  - Liu X
AD  - Howard Hughes Medical Institute and Department of Biochemistry, University of
      Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
FAU - Zou, H
AU  - Zou H
FAU - Widlak, P
AU  - Widlak P
FAU - Garrard, W
AU  - Garrard W
FAU - Wang, X
AU  - Wang X
LA  - eng
GR  - GMRO1-29935/GM/NIGMS NIH HHS/United States
GR  - GMRO1-51585/GM/NIGMS NIH HHS/United States
GR  - GMRO1-55942/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA fragmentation factor, human)
RN  - 0 (Histones)
RN  - 0 (Polymers)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.1.- (Deoxyribonucleases)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (CASP7 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 7)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - *Apoptosis
MH  - Caspase 3
MH  - Caspase 7
MH  - Caspases/metabolism
MH  - Deoxyribonucleases/*metabolism
MH  - Enzyme Activation
MH  - Histones/*metabolism
MH  - Kinetics
MH  - Plasmids/metabolism
MH  - Polymers
MH  - Protein Binding
MH  - Protein Conformation
MH  - Proteins/metabolism
MH  - Recombinant Proteins/metabolism
EDAT- 1999/05/13 00:00
MHDA- 1999/05/13 00:01
CRDT- 1999/05/13 00:00
PHST- 1999/05/13 00:00 [pubmed]
PHST- 1999/05/13 00:01 [medline]
PHST- 1999/05/13 00:00 [entrez]
AID - 10.1074/jbc.274.20.13836 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 May 14;274(20):13836-40. doi: 10.1074/jbc.274.20.13836.