Mechanism for G2 phase-specific nuclear export of the kinetochore protein CENP-F.

Published

Journal Article

Centromere protein F (CENP-F) is a component of the kinetochore and a regulator of cell cycle progression. CENP-F recruits the dynein transport machinery and orchestrates several cell cycle-specific transport events, including transport of the nucleus, mitochondria and chromosomes. A key regulatory step for several of these functions is likely the G2 phase-specific export of CENP-F from the nucleus to the cytosol, where the cytoplasmic dynein transport machinery resides; however, the molecular mechanism of this process is elusive. Here, we have identified 3 phosphorylation sites within the bipartite classical nuclear localization signal (cNLS) of CENP-F. These sites are specific for cyclin-dependent kinase 1 (Cdk1), which is active in G2 phase. Phosphomimetic mutations of these residues strongly diminish the interaction of the CENP-F cNLS with its nuclear transport receptor karyopherin α. These mutations also diminish nuclear localization of the CENP-F cNLS in cells. Notably, the cNLS is phosphorylated in the -1 position, which is important to orient the adjacent major motif for binding into its pocket on karyopherin α. We propose that localization of CENP-F is regulated by a cNLS, and a nuclear export pathway, resulting in nuclear localization during most of interphase. In G2 phase, the cNLS is weakened by phosphorylation through Cdk1, likely resulting in nuclear export of CENP-F via the still active nuclear export pathway. Once CENP-F resides in the cytosol, it can engage in pathways that are important for cell cycle progression, kinetochore assembly and the faithful segregation of chromosomes into daughter cells.

Full Text

Duke Authors

Cited Authors

  • Loftus, KM; Cui, H; Coutavas, E; King, DS; Ceravolo, A; Pereiras, D; Solmaz, SR

Published Date

  • August 3, 2017

Published In

Volume / Issue

  • 16 / 15

Start / End Page

  • 1414 - 1429

PubMed ID

  • 28723232

Pubmed Central ID

  • 28723232

Electronic International Standard Serial Number (EISSN)

  • 1551-4005

Digital Object Identifier (DOI)

  • 10.1080/15384101.2017.1338218

Language

  • eng

Conference Location

  • United States