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Multiple functions of FADD in apoptosis, NF-κB-related signaling, and heart development in Xenopus embryos.
MedLine Citation:
PMID:  23025414     Owner:  NLM     Status:  Publisher    
FADD is an adaptor protein that transmits apoptotic signals from death receptors. Additionally, FADD has been shown to play a role in various functions including cell proliferation. However, the physiological role of FADD during embryonic development remains to be delineated. Here, we show the novel roles FADD plays in development and the molecular mechanisms of these roles in Xenopus embryos. By whole-mount in situ hybridization and RT-PCR analysis, we observed that fadd is constantly expressed in early embryos. The upregulation or downregulation of FADD proteins by embryonic manipulation resulted in induction of apoptosis or size changes in the heart during development. Expression of a truncated form of FADD, FADDdd, which lacks pro-apoptotic activity, caused growth retardation of embryos associated with dramatic expressional fluctuations of genes that are regulated by NF-κB. Moreover, we isolated a homolog of mammalian cullin-4 (Cul4), a component of the ubiquitin E3 ligase family, as a FADDdd-interacting molecule in Xenopus embryos. Thus, our study shows that FADD has multiple functions in embryos; it plays a part in the regulation of NF-κB activation and heart formation, in addition to apoptosis. Furthermore, our findings provide new insights into how Cul4-based ligase is related to FADD signaling in embryogenesis.
Kazuhiro Sakamaki; Chiyo Takagi; Atsushi Kitayama; Tomoko Kurata; Takamasa S Yamamoto; Kumiko Chiba; Katsuya Kominami; Sang-Kee Jung; Katsuya Okawa; Masami Nozaki; Hiroshi Y Kubota; Naoto Ueno
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-2
Journal Detail:
Title:  Genes to cells : devoted to molecular & cellular mechanisms     Volume:  -     ISSN:  1365-2443     ISO Abbreviation:  Genes Cells     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9607379     Medline TA:  Genes Cells     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors Journal compilation © 2012 by the Molecular Biology Society of Japan/Wiley Publishing Ltd.
Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto, 606-8501, Japan.
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