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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.