title: The cyclin-dependent kinase PITSLRE/CDK11 is required for successful autophagy.
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.
authors.affiliation: Tumour Cell Death Laboratory, Beatson Institute for Cancer Research, Glasgow, UK. s.wilkinson@ed.ac.uk
authors.forename: Simon
authors.initials: S
authors.lastname: Wilkinson
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Croft
authors.forename: Jim
authors.initials: J
authors.lastname: O'Prey
authors.forename: Arenda
authors.initials: A
authors.lastname: Meedendorp
authors.forename: Margaret
authors.initials: M
authors.lastname: O'Prey
authors.forename: Christine
authors.initials: C
authors.lastname: Dufès
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Ryan
mesh_terms: D000818:Animals; D001343:Autophagy; D045744:Cell Line, Tumor; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D029721:Drosophila Proteins; C447612:CDK11a protein, human; D018844:Cyclin-Dependent Kinases