FADD Human

The Fas-Associated Death Domain (FADD) is a crucial adaptor protein involved in the regulation of apoptosis, a form of programmed cell death. Initially identified for its role in death receptor-mediated extrinsic apoptosis, FADD has since been found to participate in various non-apoptotic cellular processes, including proliferation, autophagy, and necroptosis .

FADD is a 23 kDa protein composed of 208 amino acids. It contains two main domains: the C-terminal death domain (DD) and the N-terminal death effector domain (DED). These domains, although structurally similar, have distinct functions. The DD of FADD binds to death receptors such as the Fas receptor, while the DED interacts with intracellular molecules like procaspase-8 .

Upon stimulation by the Fas ligand, the Fas receptor trimerizes, allowing FADD to bind via its DD. This interaction unmask FADD’s DED, leading to the recruitment of procaspase-8 and -10, forming the death-inducing signaling complex (DISC). This complex initiates the caspase cascade, ultimately leading to apoptosis .

Recent studies have highlighted FADD’s significant role in cancer progression. Dysregulation of FADD has been closely associated with the pathogenesis of various cancers. FADD expression and activity are modulated by a complex network of processes, including DNA methylation, non-coding RNA, and post-translational modifications . Understanding these mechanisms is crucial for developing FADD-based therapeutic strategies for cancer patients.

FADD’s involvement in both apoptotic and non-apoptotic processes makes it a potential biomarker and therapeutic target for cancer treatment. Its dysregulation in cancer suggests that targeting FADD could improve therapeutic outcomes and provide new avenues for cancer therapy .