PMID- 25285627
OWN - NLM
STAT- MEDLINE
DCOM- 20150708
LR  - 20141219
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 453
IP  - 3
DP  - 2014 Oct 24
TI  - Caspase-9 activation and Apaf-1 cleavage by MMP-3.
PG  - 563-8
LID - S0006-291X(14)01761-6 [pii]
LID - 10.1016/j.bbrc.2014.09.124 [doi]
AB  - We have previously demonstrated that matrix metalloprotease-3 (MMP-3) can act 
      inside the cell to trigger apoptosis in response to various cell stresses in 
      dopaminergic neuronal cells. However, the mechanism by which MMP-3 activity leads 
      to caspase-3 activation in apoptotic signaling was not known. In the present 
      study, we found that MMP-3 acts upstream of caspase-9. Overexpression of wild 
      type MMP-3, but not mutant MMP-3, generated the enzymatically active 35kD 
      caspase-9. The caspase-9 activation was absent in MMP-3 knockout cells, but was 
      present when these cells were transfected with wild type MMP-3 cDNA. It was 
      elevated in cells that were under a MMP-3-inducing ER stress condition, and this 
      was attenuated by pharmacologic inhibition and gene knockdown of MMP-3. 
      Incubation of recombinant catalytic domain of MMP-3 (cMMP-3) with procaspase-9 
      was not sufficient to cause caspase-9 activation, and an additional cytosolic 
      factor was required. cMMP-3 was found to bind to the cytosolic protein Apaf-1, as 
      determined by changes in surface plasmon resonance, and to cleave Apaf-1. 
      Pharmacological inhibition, knockout, and knockdown of MMP-3 attenuated the 
      cleavage. Taken together, the present study demonstrates that MMP-3 leads to 
      caspase-9 activation and suggests that this occurs indirectly via a cytosolic 
      protein, possibly involving Apaf-1.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Kim, Eun-Mee
AU  - Kim EM
AD  - Department of Emergency Medical Technology, Korea Nazarene University, Cheonan 
      331-718, South Korea.
FAU - Shin, Eun-Jung
AU  - Shin EJ
AD  - Department of Biochemistry and Molecular Biology, Cell Dysfunction Research 
      Center (CDRC), University of Ulsan College of Medicine, Seoul 138-736, South 
      Korea.
FAU - Lee, Ji Ae
AU  - Lee JA
AD  - Department of Biochemistry and Molecular Biology, Cell Dysfunction Research 
      Center (CDRC), University of Ulsan College of Medicine, Seoul 138-736, South 
      Korea.
FAU - Son, Hyo Jin
AU  - Son HJ
AD  - Department of Biochemistry and Molecular Biology, Cell Dysfunction Research 
      Center (CDRC), University of Ulsan College of Medicine, Seoul 138-736, South 
      Korea.
FAU - Choi, Dong Hee
AU  - Choi DH
AD  - Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, 
      Konkuk University, Seoul 143-747, South Korea.
FAU - Han, Ji Man
AU  - Han JM
AD  - Department of Biochemistry and Molecular Biology, Cell Dysfunction Research 
      Center (CDRC), University of Ulsan College of Medicine, Seoul 138-736, South 
      Korea.
FAU - Hwang, Onyou
AU  - Hwang O
AD  - Department of Biochemistry and Molecular Biology, Cell Dysfunction Research 
      Center (CDRC), University of Ulsan College of Medicine, Seoul 138-736, South 
      Korea. Electronic address: oyhwang@amc.seoul.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141005
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Apaf1 protein, mouse)
RN  - 0 (Apoptotic Protease-Activating Factor 1)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Apoptotic Protease-Activating Factor 1/*metabolism
MH  - Caspase 9/*metabolism
MH  - Endoplasmic Reticulum/metabolism
MH  - Enzyme Activation
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Protein Binding
MH  - Proteolysis
MH  - Signal Transduction
MH  - Stress, Physiological
MH  - Surface Plasmon Resonance
OTO - NOTNLM
OT  - Apaf-1
OT  - Apoptosis
OT  - Caspase-9
OT  - Matrix metalloproteinase-3
EDAT- 2014/10/07 06:00
MHDA- 2015/07/15 06:00
CRDT- 2014/10/07 06:00
PHST- 2014/09/25 00:00 [received]
PHST- 2014/09/27 00:00 [accepted]
PHST- 2014/10/07 06:00 [entrez]
PHST- 2014/10/07 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
AID - S0006-291X(14)01761-6 [pii]
AID - 10.1016/j.bbrc.2014.09.124 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2014 Oct 24;453(3):563-8. doi: 
      10.1016/j.bbrc.2014.09.124. Epub 2014 Oct 5.