title: 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 using autophagy is indispensable for survival. By screening known kinases in the yeast genome, we newly identified a regulator of autophagy, the Ccl1-Kin28 kinase complex (the equivalent of the 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 crucial in the assembly of the Atg1 kinase complex. The identification of this previously unknown regulatory pathway sheds new light on the complex signaling network that governs autophagy activity.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, People's Republic of China Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, People's Republic of China.
authors.forename: Shuangsheng
authors.initials: S
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, People's Republic of China.
authors.forename: Puzhong
authors.initials: P
authors.lastname: Lu
authors.affiliation: Division of Structure Biology & Biochemistry, School of Biological Sciences, Nanyang Technological University, Singapore 138673, Singapore.
authors.forename: Wenting
authors.initials: W
authors.lastname: Bu
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, People's Republic of China.
authors.forename: Tian
authors.initials: T
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, People's Republic of China liyulab@mail.tsinghua.edu.cn zxie@sjtu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China liyulab@mail.tsinghua.edu.cn zxie@sjtu.edu.cn.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Xie
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D009584:Nitrogen / Q000172:deficiency* / Q000494:pharmacology; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D051758:Transcription Factor TFIIH / Q000378:metabolism*
chemical_list: C448995:CCL1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D051758:Transcription Factor TFIIH; C000611384:KIN28 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex; D009584:Nitrogen
keywords: Autophagy; Kinase; Proteasome; Regulation; Yeast