title: The tumor suppressor proteins ASPP1 and ASPP2 interact with C-Nap1 and regulate centrosome linker reassembly.
abstract: Centrosome linker tethers interphase centrosomes together allowing them to function as a single microtubule organization center. The centrosome linker is disrupted at the onset of mitosis to ensure timely centrosome disjunction and bipolar spindle formation and is reassembled at the end of mitosis. While the mechanism controlling centrosome linker disassembly at early mitosis has been well explored, little is known about how the linker is subsequently reassembled before mitotic exit. Here we report that ASPP1 and ASPP2, two members of the apoptosis stimulating proteins of p53 (ASPP) family, are involved in centrosome linker reassembly. We showed that ASPP1/2 interacted with centrosome linker protein C-Nap1. Co-depletion of ASPP1 and ASPP2 inhibited re-association of C-Nap1 with centrosome at the end of mitosis. Moreover, ASPP1/2 facilitated the interaction between C-Nap1 and PP1α, and this interaction was significantly reduced by co-depletion of ASPP1/2. ASPP1/2 antagonized the NEK2A-mediated C-Nap1 Ser2417/2421 phosphorylation in a PP1-dependent manner. Co-depletion of ASPP1 and ASPP2 inhibited dephosphorylation of C-Nap1 (Ser2417/2421) at the end of mitosis. Based on these findings, we propose that ASPP1/2 act as PP1-targeting subunits to facilitate C-Nap1 dephosphorylation and centrosome linker reassembly at the end of mitosis.
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, PR China.
authors: Yuanyuan
authors: Y
authors: Zhang
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, PR China.
authors: Yuqi
authors: Y
authors: Wang
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, PR China.
authors: Youheng
authors: Y
authors: Wei
authors: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, PR China.
authors: Jian
authors: J
authors: Ma
authors: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, PR China.
authors: Jingtao
authors: J
authors: Peng
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, PR China.
authors: Reziya
authors: R
authors: Wumaier
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, PR China.
authors: Suqin
authors: S
authors: Shen
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, PR China; Shanghai Cancer Center, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China. Electronic address: pzzhang@fudan.edu.cn.
authors: Pingzhao
authors: P
authors: Zhang
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, PR China. Electronic address: longyu@fudan.edu.cn.
authors: Long
authors: L
authors: Yu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001324:Autoantigens / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D060066:Protein Interaction Maps
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D001324:Autoantigens; D018797:Cell Cycle Proteins; C111329:CEP250 protein, human; C498406:PPP1R13B protein, human; C090468:TP53BP2 protein, human
keywords: ASPP; C-Nap1; Centrosome linker; Mitosis; NEK2A; PP1