Regulation of Cenp-F localization to nuclear pores and kinetochores

Cell Cycle. 2018;17(17):2122-2133. doi: 10.1080/15384101.2018.1520569. Epub 2018 Sep 20.

Abstract

In metazoans, the assembly of kinetochores on centrometric chromatin and the dismantling of nuclear pore complexes are processes that have to be tightly coordinated to ensure the proper assembly of the mitotic spindle and a successful mitosis. It is therefore noteworthy that these two macromolecular assemblies share a subset of constituents. One of these multifaceted components is Cenp-F, a protein implicated in cancer and developmental pathologies. During the cell cycle, Cenp-F localizes in multiple cellular structures including the nuclear envelope in late G2/early prophase and kinetochores throughout mitosis. We recently characterized the molecular determinants of Cenp-F interaction with Nup133, a structural nuclear pore constituent. In parallel with two other independent studies, we further elucidated the mechanisms governing Cenp-F kinetochore recruitment that mainly relies on its interaction with Bub1, with redundant contribution of Cenp-E upon acute microtubule depolymerisation. Here we synthesize the current literature regarding the dual location of Cenp-F at nuclear pores and kinetochores and extend our discussion to the regulation of these NPC and kinetochore localizations by mitotic kinase and spindle microtubules.

Keywords: Bub1; Cenp-E; Cenp-F; Lek1; Mitosin; Nup133; kinetochore; nuclear pore complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Humans
  • Kinetochores / metabolism*
  • Microfilament Proteins / metabolism*
  • Microtubules / metabolism*
  • Nuclear Pore / metabolism*
  • Spindle Apparatus / metabolism

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Microfilament Proteins
  • centromere protein F

Grants and funding

This work was supported by the Centre national de la recherche scientifique (CNRS), the Fondation pour la Recherche Médicale [DEQ20150734355, “Equipe FRM 2015”]; Labex Who Am I? (ANR-11-LABX-0071; Idex ANR-11-IDEX-0005-02)[Transitional post-doc fellowship to AB]; Ligue Nationale contre le Cancer [Fourth year PhD fellowship to AB]; Ministère de l’Enseignement Supérieur et de la Recherche [PhD fellowship to AB].