The Ccl1-Kin28 kinase complex regulates autophagy under nitrogen starvation

Abstract

Starvation triggers global alterations in the synthesis and turnover of proteins. Under such conditions, the recycling of essential nutrients by autophagy is indispensable for survival. By screening known kinases in the yeast genome, we identified a novel regulator of autophagy, the Ccl1-Kin28 kinase complex (homologue of mammalian cyclin H - Cdk7 complex), which is known to play key roles in RNA polymerase II mediated transcription. We show that inactivation of Ccl1 caused complete block of autophagy. Interestingly, Ccl1 itself was subject to proteasomal degradation, limiting the level of autophagy during prolonged starvation. We present further evidence that the Ccl1-Kin28 complex regulates the expression of Atg29 and Atg31, which is critical in the assembly of the Atg1 kinase complex. The identification of this novel regulation pathway shed new lights on the complex signaling network governing autophagy activity.