The AMPK/p27Kip1 Pathway as a Novel Target to Promote Autophagy and Resilience in Aged Cells

Once believed to solely function as a cyclin-dependent kinase inhibitor, p27(Kip1) is now emerging as a critical mediator of autophagy, cytoskeletal dynamics, cell migration and apoptosis. During periods of metabolic stress, the subcellular location of p27(Kip1) largely dictates its function. Cytoplasmic p27(Kip1) has been found to be promote cellular resilience through autophagy and anti-apoptotic mechanisms. Nuclear p27(Kip1), however, inhibits cell cycle progression and makes the cell susceptible to quiescence, apoptosis, and/or senescence. Cellular location of p27(Kip1) is regulated, in part, by phosphorylation by various kinases, including Akt and AMPK. Aging promotes nuclear localization of p27(Kip1) and a predisposition to senescence or apoptosis. Here, we will review the role of p27(Kip1) in healthy and aging cells with a particular emphasis on the interplay between autophagy and apoptosis.

Automated summary

p27(Kip1) was previously thought to only act as a cyclin-dependent kinase inhibitor, but it is now recognized as a crucial mediator of various cellular processes, including autophagy, cytoskeletal dynamics, cell migration, and apoptosis. The subcellular location of p27(Kip1) plays a critical role in determining its function, with cytoplasmic p27(Kip1) promoting cellular resilience and nuclear p27(Kip1) inhibiting cell cycle progression. Regulation of p27(Kip1) cellular localization through phosphorylation by kinases like Akt and AMPK contributes to its role in aging and cell fate.