title: Multiple functions of FADD in apoptosis, NF-κB-related signaling, and heart development in Xenopus embryos.
abstract: 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.
authors.affiliation: Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto, 606-8501, Japan. ksakamak@lif.kyoto-u.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sakamaki
authors.forename: Chiyo
authors.initials: C
authors.lastname: Takagi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kitayama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kurata
authors.forename: Takamasa S
authors.initials: TS
authors.lastname: Yamamoto
authors.forename: Kumiko
authors.initials: K
authors.lastname: Chiba
authors.forename: Katsuya
authors.initials: K
authors.lastname: Kominami
authors.forename: Sang-Kee
authors.initials: SK
authors.lastname: Jung
authors.forename: Katsuya
authors.initials: K
authors.lastname: Okawa
authors.forename: Masami
authors.initials: M
authors.lastname: Nozaki
authors.forename: Hiroshi Y
authors.initials: HY
authors.lastname: Kubota
authors.forename: Naoto
authors.initials: N
authors.lastname: Ueno
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis; D001757:Blastomeres / Q000201:enzymology / Q000378:metabolism; D044842:Cullin Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006321:Heart / Q000196:embryology*; D006801:Humans; D008969:Molecular Sequence Data; D060172:Morpholinos / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism* / Q000502:physiology; D010446:Peptide Fragments / Q000737:chemistry; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D015398:Signal Transduction; D015533:Transcriptional Activation; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D044842:Cullin Proteins; D053200:Fas-Associated Death Domain Protein; D060172:Morpholinos; C499316:MyD88 protein, Xenopus; D016328:NF-kappa B; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D029867:Xenopus Proteins