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000045390 0247_ $$2pmid$$apmid:15817164
000045390 0247_ $$2DOI$$a10.1016/j.yexcr.2005.01.012
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000045390 041__ $$aeng
000045390 082__ $$a570
000045390 084__ $$2WoS$$aOncology
000045390 084__ $$2WoS$$aCell Biology
000045390 1001_ $$0P:(DE-HGF)0$$aVetterkind, S.$$b0
000045390 245__ $$aBinding of Par-4 to the actin cytoskeleton is essential for Par-4/Dlk-mediated apoptosis
000045390 260__ $$aOrlando, Fla.$$bAcademic Press$$c2005
000045390 300__ $$a392 - 408
000045390 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article
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000045390 440_0 $$013781$$aExperimental Cell Research$$v305$$x0014-4827
000045390 500__ $$aRecord converted from VDB: 12.11.2012
000045390 520__ $$aProstate apoptosis response-4 (Par-4) is a 38-kDa protein originally identified as a gene product upregulated in prostate cancer cells undergoing apoptosis. Cell death mediated by Par-4 and its interaction partner DAP like kinase (Dlk) is characterized by dramatic changes of the cytoskeleton. To uncover the role of the cytoskeleton in Par-4/Dlk-mediated apoptosis, we analyzed Par-4 for a direct association with cytoskeletal structures. Confocal fluorescence microscopy revealed that endogenous Par-4 is specifically associated with stress fibers in rat fibroblasts. In vitro cosedimentation analyses and in vivo FRET analyses showed that Par-4 directly binds to F-actin. Actin binding is mediated by the N-terminal 266 amino acids, but does not require the C-terminal region of Par-4 containing the leucine zipper and the death domain. Furthermore, the interaction of Par-4 with actin filaments leads to the formation of actin bundles in vitro and in vivo. In rat fibroblasts, this microfilament association is essential for the pro-apoptotic function of Par-4, since both disruption of the actin cytoskeleton by cytochalasin D treatment and overexpression of Par-4 constructs impaired in actin binding result in a significant decrease of apoptosis induction by Par-4 and Dlk. We propose a model, in which Par-4 recruits Dlk to stress fibers, leading to enhanced phosphorylation of the regulatory light chain of myosin II (MLC) and to the induction of apoptosis.
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000045390 650_2 $$2MeSH$$aActin Cytoskeleton: chemistry
000045390 650_2 $$2MeSH$$aActin Cytoskeleton: metabolism
000045390 650_2 $$2MeSH$$aActins: analysis
000045390 650_2 $$2MeSH$$aActins: metabolism
000045390 650_2 $$2MeSH$$aAnimals
000045390 650_2 $$2MeSH$$aApoptosis: physiology
000045390 650_2 $$2MeSH$$aApoptosis Regulatory Proteins
000045390 650_2 $$2MeSH$$aCalcium-Calmodulin-Dependent Protein Kinases
000045390 650_2 $$2MeSH$$aCardiac Myosins: metabolism
000045390 650_2 $$2MeSH$$aCell Line, Tumor
000045390 650_2 $$2MeSH$$aHumans
000045390 650_2 $$2MeSH$$aIntracellular Signaling Peptides and Proteins: analysis
000045390 650_2 $$2MeSH$$aIntracellular Signaling Peptides and Proteins: genetics
000045390 650_2 $$2MeSH$$aIntracellular Signaling Peptides and Proteins: metabolism
000045390 650_2 $$2MeSH$$aMAP Kinase Kinase Kinases
000045390 650_2 $$2MeSH$$aMale
000045390 650_2 $$2MeSH$$aMice
000045390 650_2 $$2MeSH$$aMutation: genetics
000045390 650_2 $$2MeSH$$aMyosin Light Chains: metabolism
000045390 650_2 $$2MeSH$$aPhosphorylation
000045390 650_2 $$2MeSH$$aProtein-Serine-Threonine Kinases: metabolism
000045390 650_2 $$2MeSH$$aRats
000045390 650_2 $$2MeSH$$aUp-Regulation
000045390 650_7 $$00$$2NLM Chemicals$$aActins
000045390 650_7 $$00$$2NLM Chemicals$$aApoptosis Regulatory Proteins
000045390 650_7 $$00$$2NLM Chemicals$$aIntracellular Signaling Peptides and Proteins
000045390 650_7 $$00$$2NLM Chemicals$$aMyosin Light Chains
000045390 650_7 $$00$$2NLM Chemicals$$amyosin light chain 2
000045390 650_7 $$00$$2NLM Chemicals$$aprostate apoptosis response-4 protein
000045390 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$aProtein-Serine-Threonine Kinases
000045390 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$adeath-associated protein kinase
000045390 650_7 $$0EC 2.7.11.17$$2NLM Chemicals$$aCalcium-Calmodulin-Dependent Protein Kinases
000045390 650_7 $$0EC 2.7.11.25$$2NLM Chemicals$$aMAP Kinase Kinase Kinases
000045390 650_7 $$0EC 2.7.11.25$$2NLM Chemicals$$amitogen-activated protein kinase kinase kinase 12
000045390 650_7 $$0EC 3.6.1.-$$2NLM Chemicals$$aCardiac Myosins
000045390 650_7 $$2WoSType$$aJ
000045390 65320 $$2Author$$aactin
000045390 65320 $$2Author$$acytoskeleton
000045390 65320 $$2Author$$aPar-4
000045390 65320 $$2Author$$aDlk
000045390 65320 $$2Author$$aapoptosis
000045390 7001_ $$0P:(DE-HGF)0$$aIllenberger, S.$$b1
000045390 7001_ $$0P:(DE-Juel1)VDB10481$$aKubicek, J.$$b2$$uFZJ
000045390 7001_ $$0P:(DE-HGF)0$$aBoosen, M.$$b3
000045390 7001_ $$0P:(DE-HGF)0$$aAppel, S.$$b4
000045390 7001_ $$0P:(DE-HGF)0$$aNaim, H. Y.$$b5
000045390 7001_ $$0P:(DE-HGF)0$$aScheidtmann, K.-H.$$b6
000045390 7001_ $$0P:(DE-HGF)0$$aPreuss, U.$$b7
000045390 773__ $$0PERI:(DE-600)1466780-0$$a10.1016/j.yexcr.2005.01.012$$gVol. 305, p. 392 - 408$$p392 - 408$$q305<392 - 408$$tExperimental cell research$$v305$$x0014-4827$$y2005
000045390 8567_ $$uhttp://dx.doi.org/10.1016/j.yexcr.2005.01.012
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000045390 9141_ $$y2005
000045390 915__ $$0StatID:(DE-HGF)0010$$aJCR/ISI refereed
000045390 9201_ $$0I:(DE-Juel1)VDB58$$d31.12.2006$$gIBI$$kIBI-2$$lBiologische Strukturforschung$$x0
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