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Microtubule-associated proteins 1A/1B light chain 3B (LC3) is a small, ubiquitin-like protein of 17-18 kDa widely recognized as one of the most definitive markers and central effectors of autophagy in mammalian cells. LC3 is encoded by the MAP1LC3B gene and belongs to the highly conserved ATG8 protein family, which is fundamental to autophagosome membrane formation, cargo recognition, and vesicle trafficking. During autophagy, cytosolic LC3-I is cleaved and conjugated to phosphatidylethanolamine, producing LC3-II, which is tightly bound to autophagosomal membranes and serves as the key readout for autophagic activity. Besides its structural and adaptor roles in autophagy, LC3B has RNA-binding properties and can facilitate degradation of specific mRNAs during autophagy. Mutations or dysregulation of LC3 and related ATG8 family proteins impact diverse biological processes, including mitophagy and selective substrate degradation, and are implicated in pathologies such as cancer, neurodegenerative, and cardiovascular diseases. Drugs commonly used in research, such as rapamycin, chloroquine, and bafilomycin A1, modulate LC3 conversion and turnover for autophagy studies, but LC3 is not itself a direct drug target in standard clinical therapies. The primary limitation in utilizing LC3 as a biomarker is the complex interpretation: LC3-II accumulation may indicate both enhanced autophagosome formation or impaired autophagy flux, complicating its use as a simple diagnostic tool for autophagic activity.
Autophagy induction (conversion of LC3-I to LC3-II as a hallmark of autophagy initiation), Autophagosome-lysosome fusion inhibition (as a way to modulate LC3 turnover)
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