biostudies-literatureCoryell PRNICHD NIH HHSW. M. Keck FoundationNational Institutes of HealthNIH HHSNIGMS NIH HHSe13171https://www.ebi.ac.uk/biostudies/studies/S-EPMC7370706biostudies-literatureUnknown19(7)The tumor suppressor protein p16^INK4a (p16) is a well-established hallmark of aging that induces cellular senescence in response to stress. Previous studies have focused primarily on p16 regulation at the transcriptional level; comparatively little is known about the protein's intracellular localization and degradation. The autophagy-lysosomal pathway has been implicated in the subcellular trafficking and turnover of various stress-response proteins and has also been shown to attenuate age-related pathologies, but it is unclear whether p16 is involved in this pathway. Here, we investigate the role of autophagy, vesicular trafficking, and lysosomal degradation on p16 expression and localization in human epithelial cells. Time-lapse fluorescence microscopy using an endogenous p16-Aging cellAutophagy regulates the localization and degradation of p16^INK4a.PMC7370706DP2‐HD091800T32‐GM007092DDP2-HD091800R00 GM102372R01 GM138834DP2 HD091800R00-GM102372T32-GM007092DR00‐GM102372Purvis JEGriffin KAGoraya SKRedick MASisk SRCoryell PRfalseAutophagy regulates the localization and degradation of p16^INK4a.The tumor suppressor protein p16^INK4a (p16) is a well-established hallmark of aging that induces cellular senescence in response to stress. Previous studies have focused primarily on p16 regulation at the transcriptional level; comparatively little is known about the protein's intracellular localization and degradation. The autophagy-lysosomal pathway has been implicated in the subcellular trafficking and turnover of various stress-response proteins and has also been shown to attenuate age-related pathologies, but it is unclear whether p16 is involved in this pathway. Here, we investigate the role of autophagy, vesicular trafficking, and lysosomal degradation on p16 expression and localization in human epithelial cells. Time-lapse fluorescence microscopy using an endogenous p16-2020-01-01T00:00:00Z2020 Jul2025-04-05T12:42:21.608Z2025-04-05T12:42:21.608ZS-EPMC73707063266224410.1111/acel.13171