%0 Journal Article
%A Vetterkind, S.
%A Illenberger, S.
%A Kubicek, J.
%A Boosen, M.
%A Appel, S.
%A Naim, H. Y.
%A Scheidtmann, K.-H.
%A Preuss, U.
%T Binding of Par-4 to the actin cytoskeleton is essential for Par-4/Dlk-mediated apoptosis
%J Experimental cell research
%V 305
%@ 0014-4827
%C Orlando, Fla.
%I Academic Press
%M PreJuSER-45390
%P 392 - 408
%D 2005
%Z Record converted from VDB: 12.11.2012
%X 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.
%K Actin Cytoskeleton: chemistry
%K Actin Cytoskeleton: metabolism
%K Actins: analysis
%K Actins: metabolism
%K Animals
%K Apoptosis: physiology
%K Apoptosis Regulatory Proteins
%K Calcium-Calmodulin-Dependent Protein Kinases
%K Cardiac Myosins: metabolism
%K Cell Line, Tumor
%K Humans
%K Intracellular Signaling Peptides and Proteins: analysis
%K Intracellular Signaling Peptides and Proteins: genetics
%K Intracellular Signaling Peptides and Proteins: metabolism
%K MAP Kinase Kinase Kinases
%K Male
%K Mice
%K Mutation: genetics
%K Myosin Light Chains: metabolism
%K Phosphorylation
%K Protein-Serine-Threonine Kinases: metabolism
%K Rats
%K Up-Regulation
%K Actins (NLM Chemicals)
%K Apoptosis Regulatory Proteins (NLM Chemicals)
%K Intracellular Signaling Peptides and Proteins (NLM Chemicals)
%K Myosin Light Chains (NLM Chemicals)
%K myosin light chain 2 (NLM Chemicals)
%K prostate apoptosis response-4 protein (NLM Chemicals)
%K Protein-Serine-Threonine Kinases (NLM Chemicals)
%K death-associated protein kinase (NLM Chemicals)
%K Calcium-Calmodulin-Dependent Protein Kinases (NLM Chemicals)
%K MAP Kinase Kinase Kinases (NLM Chemicals)
%K mitogen-activated protein kinase kinase kinase 12 (NLM Chemicals)
%K Cardiac Myosins (NLM Chemicals)
%K J (WoSType)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:15817164
%U <Go to ISI:>//WOS:000228409100016
%R 10.1016/j.yexcr.2005.01.012
%U https://juser.fz-juelich.de/record/45390