title: The 68-kDa telomeric repeat binding factor 1 (TRF1)-associated protein (TAP68) interacts with and recruits TRF1 to the spindle pole during mitosis.
abstract: The telomere capping protein TRF1 is a component of the multiprotein complex "shelterin," which organizes the telomere into a high order structure. Besides telomere maintenance, telomere-associated proteins also have nontelomeric functions. For example, tankyrase 1 and TRF1 are required for the maintenance of faithful mitotic progression. However, the functional relevance of their centrosomal localization has not been established. Here, we report the identification of a TRF1-binding protein, TAP68, that interacts with TRF1 in mitotic cells. TAP68 contains two coiled-coil domains and a structural maintenance of chromosome motifs and co-localizes with TRF1 to telomeres during interphase. Immediately after nuclear envelope breakdown, TAP68 translocates toward the spindle poles followed by TRF1. Dissociation of TAP68 from the telomere is concurrent with the Nek2A-dependent phosphorylation at Thr-221. Biochemical characterization demonstrated that the first coiled-coil domain of TAP68 binds and recruits TRF1 to the centrosome. Inhibition of TAP68 expression by siRNA blocked the localization of TRF1 and tankyrase 1 to the centrosome. Furthermore, siRNA-mediated depletion of TAP68 perturbed faithful chromosome segregation and genomic stability. These findings suggest that TAP68 functions in mediating TRF1-tankyrase 1 localization to the centrosome and in mitotic regulation.
authors.affiliation: From the Department of Hematology and Hematopoietic Stem Cell Transplant Center, Zhejiang Provincial People's Hospital, Hangzhou 310014.
authors.forename: Jianping
authors.initials: J
authors.lastname: Lan
authors.affiliation: the Department of Hematology and Bone Marrow Transplant Center, 1st Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, and.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: the Anhui Key Laboratory of Cellular Dynamics and Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Xu
authors.affiliation: the Anhui Key Laboratory of Cellular Dynamics and Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Yu
authors.affiliation: the Department of Hematology and Bone Marrow Transplant Center, 1st Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, and.
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.affiliation: the Anhui Key Laboratory of Cellular Dynamics and Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: the Anhui Key Laboratory of Cellular Dynamics and Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Chuanhai
authors.initials: C
authors.lastname: Fu
authors.affiliation: From the Department of Hematology and Hematopoietic Stem Cell Transplant Center, Zhejiang Provincial People's Hospital, Hangzhou 310014.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Wang
authors.affiliation: the Anhui Key Laboratory of Cellular Dynamics and Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Ke
authors.affiliation: the Department of Hematology and Bone Marrow Transplant Center, 1st Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, and hehuangyu@126.com.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: the Anhui Key Laboratory of Cellular Dynamics and Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei 230027, China douzhen@ustc.edu.cn.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dou
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007399:Interphase; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D008938:Mitosis; D008969:Molecular Sequence Data; D000072379:NIMA-Related Kinases; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D064047:Spindle Poles / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D008840:Microfilament Proteins; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D035321:Telomeric Repeat Binding Protein 1; D000097869:Polo-Like Kinase 1; C425471:TRIOBP protein, human; C089441:NEK2 protein, human
keywords: Cell Biology; Centriole; Mitosis; Nek2A Kinase; Phosphorylation; TAP68; TRF1; Telomeres