CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment

EMBO J. 2011 Jan 5;30(1):130-44. doi: 10.1038/emboj.2010.276. Epub 2010 Nov 9.

Abstract

Proper attachment of microtubules to kinetochores is essential for accurate chromosome segregation. Here, we report a novel protein involved in kinetochore-microtubule attachment, chromosome alignment-maintaining phosphoprotein (CAMP) (C13orf8, ZNF828). CAMP is a zinc-finger protein containing three characteristic repeat motifs termed the WK, SPE, and FPE motifs. CAMP localizes to chromosomes and the spindle including kinetochores, and undergoes CDK1-dependent phosphorylation at multiple sites during mitosis. CAMP-depleted cells showed severe chromosome misalignment, which was associated with the poor resistance of K-fibres to the tension exerted upon establishment of sister kinetochore bi-orientation. We found that the FPE region, which is responsible for spindle and kinetochore localization, is essential for proper chromosome alignment. The C-terminal region containing the zinc-finger domains negatively regulates chromosome alignment, and phosphorylation in the FPE region counteracts this regulation. Kinetochore localization of CENP-E and CENP-F was affected by CAMP depletion, and by expressing CAMP mutants that cannot functionally rescue CAMP depletion, placing CENP-E and CENP-F as downstream effectors of CAMP. These data suggest that CAMP is required for maintaining kinetochore-microtubule attachment during bi-orientation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomal Proteins, Non-Histone / analysis
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosomes, Human
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism*
  • Kinetochores / ultrastructure
  • Mad2 Proteins
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Mitosis
  • Phosphoproteins / analysis
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Proteins / metabolism
  • RNA Interference
  • Spindle Apparatus / ultrastructure

Substances

  • CHAMP1 protein, human
  • Chromosomal Proteins, Non-Histone
  • MAD2L2 protein, human
  • Mad2 Proteins
  • Phosphoproteins
  • Proteins