The 68-kDa telomeric repeat binding factor 1 (TRF1)-associated protein (TAP68) interacts with and recruits TRF1 to the spindle pole during mitosis

J Biol Chem. 2014 May 16;289(20):14145-56. doi: 10.1074/jbc.M113.526244. Epub 2014 Apr 1.

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.

Keywords: Cell Biology; Centriole; Mitosis; Nek2A Kinase; Phosphorylation; TAP68; TRF1; Telomeres.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Cycle Proteins / metabolism
  • Centrosome / metabolism
  • HeLa Cells
  • Humans
  • Interphase
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / metabolism*
  • Mitosis*
  • Molecular Sequence Data
  • NIMA-Related Kinases
  • Phosphorylation
  • Protein Binding
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Structure, Tertiary
  • Protein Transport
  • Proto-Oncogene Proteins / metabolism
  • Spindle Poles / metabolism*
  • Telomere / metabolism
  • Telomeric Repeat Binding Protein 1 / metabolism*

Substances

  • Cell Cycle Proteins
  • Microfilament Proteins
  • Proto-Oncogene Proteins
  • TRIOBP protein, human
  • Telomeric Repeat Binding Protein 1
  • NEK2 protein, human
  • NIMA-Related Kinases
  • Protein Serine-Threonine Kinases
  • polo-like kinase 1