| FADD-calmodulin interaction: a novel player in cell cycle regulation. | |
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MedLine Citation:
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PMID: 20420860 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 (CKIalpha), has been shown to regulate FADD-dependent non-apoptotic activities. Remarkably, we showed that both FADD and CaM are CKIalpha substrates and that in synchronized HeLa cells, FADD, CaM and CKIalpha 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 CKIalpha may have an important role in the regulation of cell fate. |
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Authors:
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Giuliana Papoff; Nadia Trivieri; Roberta Crielesi; Francesca Ruberti; Sonia Marsilio; Giovina Ruberti |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-24 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1803 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-06-14 Completed Date: 2010-09-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 898-911 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Istituto di Biologia Cellulare, Consiglio Nazionale delle Ricerche, Campus A. Buzzati-Traverso, Monterotondo, Rome, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calmodulin / genetics, metabolism* Casein Kinase Ialpha / genetics, metabolism Cell Cycle / drug effects, physiology* Cell Line Fas-Associated Death Domain Protein / genetics, metabolism* Humans Mice Mitotic Spindle Apparatus / metabolism Mutation Paclitaxel / pharmacology Protein Binding Protein Interaction Mapping Protein Structure, Tertiary Recombinant Fusion Proteins / genetics, metabolism Tubulin Modulators / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Calmodulin; 0/Fas-Associated Death Domain Protein; 0/Recombinant Fusion Proteins; 0/Tubulin Modulators; 33069-62-4/Paclitaxel; EC 2.7.11.1/Casein Kinase Ialpha |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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