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The cyclin-dependent kinase PITSLRE/CDK11 is required for successful autophagy

Wilkinson, Simon and Croft, Daniel and O’Prey, Jim and Meedendorp, Arenda and O’Prey, Margaret and Dufès, Christine and Ryan, Kevin M. (2011) The cyclin-dependent kinase PITSLRE/CDK11 is required for successful autophagy. Autophagy, 7 (11). pp. 1295-1301.

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Abstract

(Macro)autophagy is a membrane-trafficking process that serves to sequester cellular constituents in organelles termed autophagosomes, which target their degradation in the lysosome. Autophagy operates at basal levels in all cells where it serves as a homeostatic mechanism to maintain cellular integrity. The levels and cargoes of autophagy can, however, change in response to a variety of stimuli, and perturbations in autophagy are known to be involved in the aetiology of various human diseases. Autophagy must therefore be tightly controlled. We report here that the Drosophila cyclin-dependent kinase PITSLRE is a modulator of autophagy. Loss of the human PITSLRE orthologue, CDK11, initially appears to induce autophagy, but at later time points CDK11 is critically required for autophagic flux and cargo digestion. Since PITSLRE/CDK11 regulates autophagy in both Drosophila and human cells, this kinase represents a novel phylogenetically conserved component of the autophagy machinery.