کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10905340 | 1086746 | 2005 | 17 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Binding of Par-4 to the actin cytoskeleton is essential for Par-4/Dlk-mediated apoptosis
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کلمات کلیدی
GFPSACDAP-kinaseDLKCytDPAR-4 - BY-4actin - اکتین death domain - حوزه مرگApoptosis - خزان یاختهایleucine zipper - زیپ لوسینcytochalasin D - سیتوکالازین DNOC - شبnocodazole - نوکودازولgreen fluorescent protein - پروتئین فلورسنت سبزdeath-associated protein kinase - پروتئین کیناز وابسته به مرگCytoskeleton - چارچوب یاخته، سیتواسکلتون، اسکلت سلولی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 305, Issue 2, 1 May 2005, Pages 392-408
Journal: Experimental Cell Research - Volume 305, Issue 2, 1 May 2005, Pages 392-408
نویسندگان
Susanne Vetterkind, Susanne Illenberger, Jan Kubicek, Meike Boosen, Sarah Appel, Hassan Y. Naim, Karl-Heinz Scheidtmann, Ute Preuss,