Intertwined control of the cell cycle and nucleocytoplasmic transport by the cyclin-dependent kinase Pho85 and RanGTPase Gsp1 in Saccharomyces cerevisiae

Microbiol Res. 2018 Jan:206:168-176. doi: 10.1016/j.micres.2017.10.008. Epub 2017 Oct 26.

Abstract

Deciphering the molecular mechanisms that connect cell cycle progression and nucleocytoplasmic transport is of particular interest: this intertwined relationship, once understood, may provide useful insight on the diseases resulting from the malfunction of these processes. In the present study we report on findings that indicate a biochemical connection between the cell cycle regulator CDK Pho85 and Ran-GTPase Gsp1, an essential nucleocytoplasmic transport component. When Gsp1 cannot be phosphorylated by Pho85, the cell cycle progression is impaired. Accordingly, a nonphosphorylatable version of Gsp1 abnormally localizes to the nucleus, which impairs the nuclear transport of molecules, including key components of cell cycle progression. Furthermore, our results suggest that the physical interaction of Gsp1 and the Kap95 karyopherin, essential to the release of nuclear cargoes, is altered. Altogether, the present findings point to the involvement of a biochemical mechanism in the interlocked regulation of the cell cycle and nuclear transport.

Keywords: Cell cycle; Gsp1; Pho85; RAN-GTP; Saccharomyces cerevisiae.

MeSH terms

  • Active Transport, Cell Nucleus / physiology*
  • Base Sequence
  • Cell Cycle / physiology*
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism*
  • Escherichia coli / genetics
  • Homologous Recombination
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism*
  • Mutagenesis, Site-Directed
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Recombinant Proteins
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • GSP1 protein, S cerevisiae
  • Nuclear Proteins
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Cyclin-Dependent Kinases
  • PHO85 protein, S cerevisiae
  • Monomeric GTP-Binding Proteins