Fernández-Lázaro, D.; Sanz, B.; Seco-Calvo, J. The Mechanisms of Regulated Cell Death: Structural and Functional Proteomic Pathways Induced or Inhibited by a Specific Protein—A Narrative Review. Proteomes2024, 12, 3.
Fernández-Lázaro, D.; Sanz, B.; Seco-Calvo, J. The Mechanisms of Regulated Cell Death: Structural and Functional Proteomic Pathways Induced or Inhibited by a Specific Protein—A Narrative Review. Proteomes 2024, 12, 3.
Fernández-Lázaro, D.; Sanz, B.; Seco-Calvo, J. The Mechanisms of Regulated Cell Death: Structural and Functional Proteomic Pathways Induced or Inhibited by a Specific Protein—A Narrative Review. Proteomes2024, 12, 3.
Fernández-Lázaro, D.; Sanz, B.; Seco-Calvo, J. The Mechanisms of Regulated Cell Death: Structural and Functional Proteomic Pathways Induced or Inhibited by a Specific Protein—A Narrative Review. Proteomes 2024, 12, 3.
Abstract
Apoptosis, necroptosis, and autophagy are cellular mechanisms by which cells are programmed to die under a wide range of physiological and developmental stimuli. A multitude of protein mediators of programmed cell death have been identified and apoptosis, necroptosis, and autophagy signals have been found to utilize common pathways elucidating the proteins involved. This narrative review focuses on caspase-dependent and caspase-independent programmed cell death systems. Included studies of caspase-dependent programmed cell death include extrinsic pathway apoptotic mechanisms including phosphatidylserine (PS), FAS (APO-1/CD95), Tumor Necrosis Factor (TNF) Receptor type 1 (TNF-R1) and TNF-Related Apoptosis-Inducing Ligand (TRAIL) and intrinsic or mitochondrial pathway such as Cytochrome C, the Bcl-2 family of proteins and Smac/Diablo. The Bcl-2 family has apoptotic mediators Bcl-2-associated X protein (Bax) and Bcl-2 homologous antagonist/killer (Bak), Bcl-2-Interacting Protein BIM (Bim), Bcl-2 agonist of cell death (Bad), Bid, Bcl-2 adenovirus E1B 19kDa-interacting protein 1 NIP3 (Bnip3), BMF, HRK, Noxa and PUMA and anti-apoptotic proteins such as Bcl-2 itself, Mcl-1, Bcl-w, A1, and Bcl-XL. Moreover, caspase-independent programmed cell death pathways include the mitochondrial pathway with the protein mediators Apoptosis Inducing Factor (AIF), and Endonuclease G, the pathways Necroptosis, and Autophagy. Understanding programmed cell death from those reported in this review could shed substantial light on the processes of biological homeostasis. In addition, identifying specific proteins involved in these processes is mandatory to identify molecular biomarkers as well as therapeutic targets. This knowledge could provide the ability to modulate the programmed cell death response and could lead to new therapeutic interventions in a wide range of diseases.
Biology and Life Sciences, Cell and Developmental Biology
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