TY  - JOUR
AU  - Vetterkind, S.
AU  - Illenberger, S.
AU  - Kubicek, J.
AU  - Boosen, M.
AU  - Appel, S.
AU  - Naim, H. Y.
AU  - Scheidtmann, K.-H.
AU  - Preuss, U.
TI  - Binding of Par-4 to the actin cytoskeleton is essential for Par-4/Dlk-mediated apoptosis
JO  - Experimental cell research
VL  - 305
SN  - 0014-4827
CY  - Orlando, Fla.
PB  - Academic Press
M1  - PreJuSER-45390
SP  - 392 - 408
PY  - 2005
N1  - Record converted from VDB: 12.11.2012
AB  - Prostate apoptosis response-4 (Par-4) is a 38-kDa protein originally identified as a gene product upregulated in prostate cancer cells undergoing apoptosis. Cell death mediated by Par-4 and its interaction partner DAP like kinase (Dlk) is characterized by dramatic changes of the cytoskeleton. To uncover the role of the cytoskeleton in Par-4/Dlk-mediated apoptosis, we analyzed Par-4 for a direct association with cytoskeletal structures. Confocal fluorescence microscopy revealed that endogenous Par-4 is specifically associated with stress fibers in rat fibroblasts. In vitro cosedimentation analyses and in vivo FRET analyses showed that Par-4 directly binds to F-actin. Actin binding is mediated by the N-terminal 266 amino acids, but does not require the C-terminal region of Par-4 containing the leucine zipper and the death domain. Furthermore, the interaction of Par-4 with actin filaments leads to the formation of actin bundles in vitro and in vivo. In rat fibroblasts, this microfilament association is essential for the pro-apoptotic function of Par-4, since both disruption of the actin cytoskeleton by cytochalasin D treatment and overexpression of Par-4 constructs impaired in actin binding result in a significant decrease of apoptosis induction by Par-4 and Dlk. We propose a model, in which Par-4 recruits Dlk to stress fibers, leading to enhanced phosphorylation of the regulatory light chain of myosin II (MLC) and to the induction of apoptosis.
KW  - Actin Cytoskeleton: chemistry
KW  - Actin Cytoskeleton: metabolism
KW  - Actins: analysis
KW  - Actins: metabolism
KW  - Animals
KW  - Apoptosis: physiology
KW  - Apoptosis Regulatory Proteins
KW  - Calcium-Calmodulin-Dependent Protein Kinases
KW  - Cardiac Myosins: metabolism
KW  - Cell Line, Tumor
KW  - Humans
KW  - Intracellular Signaling Peptides and Proteins: analysis
KW  - Intracellular Signaling Peptides and Proteins: genetics
KW  - Intracellular Signaling Peptides and Proteins: metabolism
KW  - MAP Kinase Kinase Kinases
KW  - Male
KW  - Mice
KW  - Mutation: genetics
KW  - Myosin Light Chains: metabolism
KW  - Phosphorylation
KW  - Protein-Serine-Threonine Kinases: metabolism
KW  - Rats
KW  - Up-Regulation
KW  - Actins (NLM Chemicals)
KW  - Apoptosis Regulatory Proteins (NLM Chemicals)
KW  - Intracellular Signaling Peptides and Proteins (NLM Chemicals)
KW  - Myosin Light Chains (NLM Chemicals)
KW  - myosin light chain 2 (NLM Chemicals)
KW  - prostate apoptosis response-4 protein (NLM Chemicals)
KW  - Protein-Serine-Threonine Kinases (NLM Chemicals)
KW  - death-associated protein kinase (NLM Chemicals)
KW  - Calcium-Calmodulin-Dependent Protein Kinases (NLM Chemicals)
KW  - MAP Kinase Kinase Kinases (NLM Chemicals)
KW  - mitogen-activated protein kinase kinase kinase 12 (NLM Chemicals)
KW  - Cardiac Myosins (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:15817164
UR  - <Go to ISI:>//WOS:000228409100016
DO  - DOI:10.1016/j.yexcr.2005.01.012
UR  - https://juser.fz-juelich.de/record/45390
ER  -