title: Sequential phosphorylation of Nedd1 by Cdk1 and Plk1 is required for targeting of the gammaTuRC to the centrosome.
abstract: Nedd1 is a new member of the gamma-tubulin ring complex (gammaTuRC) and targets the gammaTuRC to the centrosomes for microtubule nucleation and spindle assembly in mitosis. Although its role is known, its functional regulation mechanism remains unclear. Here we report that the function of Nedd1 is regulated by Cdk1 and Plk1. During mitosis, Nedd1 is firstly phosphorylated at T550 by Cdk1, which creates a binding site for the polo-box domain of Plk1. Then, Nedd1 is further phosphorylated by Plk1 at four sites: T382, S397, S637 and S426. The sequential phosphorylation of Nedd1 by Cdk1 and Plk1 promotes its interaction with gamma-tubulin for targeting the gammaTuRC to the centrosome and is important for spindle formation. Knockdown of Plk1 by RNAi decreases Nedd1 phosphorylation and attenuates Nedd1 accumulation at the spindle pole and subsequent gamma-tubulin recruitment at the spindle pole for microtubule nucleation. Taken together, we propose that the sequential phosphorylation of Nedd1 by Cdk1 and Plk1 plays a pivotal role in targeting gammaTuRC to the centrosome by promoting the interaction of Nedd1 with the gammaTuRC component gamma-tubulin, during mitosis.
authors.affiliation: The MOE Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Bio-membrane and Membrane Bio-engineering, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.forename: Jia
authors.initials: J
authors.lastname: Feng
authors.forename: Junjie
authors.initials: J
authors.lastname: Hou
authors.forename: Fuquan
authors.initials: F
authors.lastname: Yang
authors.forename: Junjun
authors.initials: J
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
authors.forename: Chuanmao
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D008941:Spindle Apparatus / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D014404:Tubulin; D000097869:Polo-Like Kinase 1; C509189:NEDD1 protein, human