Identification of a subunit of a novel Kleisin-beta/SMC complex as a potential substrate of protein phosphatase 2A

Curr Biol. 2003 Dec 2;13(23):2058-64. doi: 10.1016/j.cub.2003.10.032.

Abstract

Protein phosphatase 2A (PP2A) holoenzymes consist of a catalytic C subunit, a scaffolding A subunit, and one of several regulatory B subunits that recruit the AC dimer to substrates. PP2A is required for chromosome segregation, but PP2A's substrates in this process remain unknown. To identify PP2A substrates, we carried out a two-hybrid screen with the regulatory B/PR55 subunit. We isolated a human homolog of C. elegans HCP6, a protein distantly related to the condensin subunit hCAP-D2, and we named this homolog hHCP-6. Both C. elegans HCP-6 and condensin are required for chromosome organization and segregation. HCP-6 binding partners are unknown, whereas condensin is composed of the structural maintenance of chromosomes proteins SMC2 and SMC4 and of three non-SMC subunits. Here we show that hHCP-6 becomes phosphorylated during mitosis and that its dephosphorylation by PP2A in vitro depends on B/PR55, suggesting that hHCP-6 is a B/PR55-specific substrate of PP2A. Unlike condensin, hHCP-6 is localized in the nucleus in interphase, but similar to condensin, hHCP-6 associates with chromosomes during mitosis. hHCP-6 is part of a complex that contains SMC2, SMC4, kleisin-beta, and the previously uncharacterized HEAT repeat protein FLJ20311. hHCP-6 is therefore part of a condensin-related complex that associates with chromosomes in mitosis and may be regulated by PP2A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Chromosome Mapping
  • Chromosome Segregation / physiology*
  • DNA-Binding Proteins / metabolism*
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Immunoblotting
  • Multiprotein Complexes
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation
  • Precipitin Tests
  • Protein Phosphatase 2
  • Substrate Specificity

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • condensin complexes
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2
  • Adenosine Triphosphatases