کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1950985 1055730 2010 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
FADD–calmodulin interaction: A novel player in cell cycle regulation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
FADD–calmodulin interaction: A novel player in cell cycle regulation
چکیده انگلیسی

Analyses of knockout and mutant transgenic mice as well as in vitro studies demonstrated a complex role of FADD in the regulation of cell fate. FADD is involved in death receptor induced apoptosis, cell cycle progression and cell proliferation. In a search for mechanisms that might regulate FADD functions, we identified, upon the screening of a lambda-phage cDNA library, calmodulin (CaM) as a novel FADD interacting protein. CaM is a key mediator of signals by the secondary messenger calcium and it is an essential regulator of cell cycle progression and cell survival. Here, we describe the identification and characterization of two calcium dependent CaM binding sites in the alpha helices 8–9 and 10–11 of FADD. Phosphorylation of human FADD at the C-terminal serine 194, by casein kinase I alpha (CKIα), has been shown to regulate FADD-dependent non-apoptotic activities. Remarkably, we showed that both FADD and CaM are CKIα substrates and that in synchronized HeLa cells, FADD, CaM and CKIα co-localize at the mitotic spindle in metaphase and anaphase. Moreover, complementation experiments in Jurkat FADD−/− T cells indicated that: a) cells expressing FADD mutants in the CaM binding sites are protected from Taxol-induced G2/M cell cycle arrest; b) FADD/CaM interaction is not required for Fas receptor-mediated apoptosis although Fas and CaM might compete for binding to FADD. We suggest that the interplay of FADD, CaM and CKIα may have an important role in the regulation of cell fate.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1803, Issue 8, August 2010, Pages 898–911
نویسندگان
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