Current Biology
Volume 13, Issue 23, 2 December 2003, Pages 2058-2064
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Identification of a Subunit of a Novel Kleisin-β/SMC Complex as a Potential Substrate of Protein Phosphatase 2A

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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 1, 2. PP2A is required for chromosome segregation 3, 4, 5, 6, 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 7, 8, 9, 10, 11. 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 [12]. 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-β, 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.

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4

These authors contributed equally to this work.

6

Present address: Department of Biochemistry, National University of Singapore, 8 Medical Drive, Singapore 117597.

5

Present address: Department of Obstetrics and Gynecology, University of Vienna, Währinger Guertel 18-20, A-1090, Vienna, Austria.