title: Phosphorylation of cyclin Y by CDK14 induces its ubiquitination and degradation.
abstract: Cyclin Y, a membrane associated cyclin, is capable of binding and activating CDK14. Here we report that human cyclin Y (CCNY) is a phosphoprotein in vivo and that phosphorylation of CCNY by CDK14 triggers its ubiquitination and degradation. Inactivation of either CDK14 or Cul1 results in accumulation of CCNY. An in vivo and in vitro mapping of CCNY phosphorylation sites by mass spectrometry revealed that the flanking regions of the conserved cyclin box are heavily phosphorylated. Phosphorylation of CCNY at Serines 71 and 73 creates a putative phospho-degron that controls its association with an SCF complex. Mutation of serine to alanine at these two sites stabilized CCNY and enhanced the activity of CCNY/CDK14 on phosphorylation of LRP6. Our results provide insight into autoregulation of the cyclin Y/CDK14 pair in CDK14 activation and cyclin Y turnover which is a process that is involved in membrane proximal signaling.
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
authors.forename: Liyong
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
authors.forename: Xueliang
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China. Electronic address: jychen@sibcb.ac.cn.
authors.forename: Jiangye
authors.initials: J
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D016213:Cyclins / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D055550:Protein Stability; D059748:Proteolysis; D054875:Ubiquitination
chemical_list: C543319:CCNY protein, human; D016213:Cyclins; C515076:CDK14 protein, human; D018844:Cyclin-Dependent Kinases; D046988:Proteasome Endopeptidase Complex
keywords: CDK14; Cyclin Y; Phosphorylation; Protein turnover; Ubiquitination