The Ki-67 Protein Interacts With Members of the Heterochromatin Protein 1 (HP1) Family: A Potential Role in the Regulation of Higher-Order Chromatin Structure

J Pathol. 2002 Feb;196(2):135-44. doi: 10.1002/path.1016.

Abstract

The expression of the nuclear protein Ki-67 (pKi-67) is strictly correlated with cell proliferation. Because of this, anti-Ki-67 antibodies can be used as operational markers to estimate the growth fraction of human neoplasia in situ. For a variety of tumours, the assessment of pKi-67 expression has repeatedly been proven to be of prognostic value for survival and tumour recurrence, but no cellular function has yet been ascribed to the Ki-67 protein. This study shows that a C-terminal domain of pKi-67 (Kon21) is able to bind to all three members of the mammalian heterochromatin protein 1 (HP1) family in vitro and in vivo. This interaction can be manipulated in living cells, as evidenced by ectopic expression of GFP-tagged HP1 proteins in HeLa cells, which results in a dramatic relocalization of endogenous pKi-67. Taken together, the data presented in this study suggest a role for pKi-67 in the control of higher-order chromatin structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division
  • Cell Nucleus / metabolism*
  • Chromatin / ultrastructure*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Fluorescent Antibody Technique
  • Green Fluorescent Proteins
  • HeLa Cells
  • Humans
  • Interphase
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism*
  • Luminescent Proteins / genetics
  • Protein Isoforms / metabolism
  • Recombinant Fusion Proteins / genetics
  • Transfection
  • Two-Hybrid System Techniques

Substances

  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Ki-67 Antigen
  • Luminescent Proteins
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • heterochromatin-specific nonhistone chromosomal protein HP-1
  • Green Fluorescent Proteins