AIM As technological interventions treating acute myocardial infarction (MI) improve, post-ischemic heart failure increasingly threatens patient health. The aim of the current study was to test whether FADD could be a potential target of gene therapy in the treatment of heart failure. METHODS Cardiomyocyte-specific FADD knockout mice along with non-transgenic littermates (NLC) were subjected ...

FadD catalyses the first step in E. coli beta-oxidation, the activation of free fatty acids into acyl-CoA thioesters. This activation makes fatty acids competent for catabolism and reduction into derivatives like alcohols and alkanes. Alcohols and alkanes derived from medium chain fatty acids (MCFAs, 6-12 carbons) are potential biofuels; however, FadD has low activity on MCFAs. Herein, we gener...

The cytoplasmic adaptor protein FADD is an essential component of the death-inducing signaling complexes (DISCs) that assemble when TNF receptor family members, such as Fas, are ligated. FADD inititates the proteolytic cascade that leads to apoptosis by binding to and promoting the autocatalytic activation of caspase-8 [1-4]. Surprisingly, FADD (but not caspase-8) is also required for T cells t...

FADD, a classical apoptotic signaling adaptor, was recently reported to have non-apoptotic functions. Here, we report the discovery that FADD regulates lipid metabolism. PPAR-α is a dietary lipid sensor, whose activation results in hypolipidemic effects. We show that FADD interacts with RIP140, which is a corepressor for PPAR-α, and FADD phosphorylation-mimic mutation (FADD-D) or FADD deficienc...

To identify essential components of the Fas-induced apoptotic signaling pathway, Jurkat T lymphocytes were chemically mutagenized and selected for clones that were resistant to Fas-induced apoptosis. We obtained five cell lines that contain mutations in the adaptor FADD. All five cell lines did not express FADD by immunoblot analysis and were completely resistant to Fas-induced death. Complemen...

Fas-associated death domain protein (FADD) is an adaptor protein bridging death receptors with initiator caspases. Thus, its function and localization are assumed to be cytoplasmic, although the localization of endogenous FADD has not been reported. Surprisingly, the data presented here demonstrate that FADD is mainly nuclear in several adherent cell lines. Its accumulation in the nucleus and e...

Cell death is an important mechanism to limit uncontrolled T-cell expansion during immune responses. Given the role of death-receptor adapter protein Fas-associated death domain (FADD) in apoptosis, it is intriguing that T-cell receptor (TCR)-induced proliferation is blocked in FADD-defective T cells. Necroptosis is an alternate form of death that can be induced by death receptors and is linked...

MLKL, a key component downstream of RIPK3, is suggested to be a terminal executor of necroptosis. Genetic studies have revealed that Ripk3 ablation rescues embryonic lethality in Fadd- or Caspase-8-deficient mice. Given that RIPK3 has also been implicated in non-necroptotic pathways including apoptosis and inflammatory signaling, it remains unclear whether the lethality in Fadd(-/-) mice is ind...

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a member of the tumor necrosis factor family that can kill a wide variety of tumor cells but not normal cells. TRAIL-induced apoptosis in humans is mediated by its receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2). What constitutes the signaling molecules downstream of these receptors, however, remains highly controversial. Using the ...

FADD (Fas-associated protein with death domain) is a classical adaptor protein in apoptosis. Increasing evidences have shown that FADD is also implicated in cell cycle progression, proliferation and tumorigenesis. The role of FADD in cancer remains largely unexplored. In this study, In Silico Analysis using Oncomine and Kaplan Meier plotter revealed that FADD is significantly up-regulated in br...