The location of pKi67 in the outer dense fibrillary compartment of the nucleolus points to a role in ribosome biogenesis during the cell division cycle

J Pathol. 2000 Apr;190(5):537-44. doi: 10.1002/(SICI)1096-9896(200004)190:5<537::AID-PATH577>3.0.CO;2-W.

Abstract

Although widely used as a marker of cell proliferation, the biochemical properties and function of the Ki67 antigen remain poorly understood. Recent data indicate that it can interact with RNA, DNA, and a number of cellular proteins including elements of the ubiquitin proteolytic pathway and a novel kinase. The evidence for its expression only in cycling cells is extensive and it is not regulated by stress, apoptosis or DNA damage. It was reasoned that a detailed characterization of the localization of pKi67 and analysis of its spatial relationship to other nucleolar proteins may provide insights into its function. Using high-resolution laser scanning confocal microscopy with double and triple labelling, pKi67 expression in MCF7 cells has been defined in relation to the distribution of nucleolin, fibrillarin, p130 (human Nopp 140 homologue), p120 (Nol 1), RH-II/Gu helicase, and topoisomerase II beta. All of these molecules are perichromosomal during mitosis and all but fibrillarin and p130 show extra-nucleolar distribution in early G1. The majority of p120 (Nol 1) and RH-II/Gu helicase co-localize in the diffuse fibrillar centre (DFC) of nucleoli, while there is only partial overlap with nucleolin and fibrillarin. There is no co-localization between p130 and pKi67. These data refine current understanding of the distribution of pKi67 and its physical relationship with functional domains of the nucleolus and place pKi67 in a zone of the DFC associated with late rRNA processing. Taken together with recent biochemical data, these observations allow the proposal of a model of pKi67 function in which it acts as an 'efficiency factor' in ribosome biogenesis during the heavy metabolic demands placed on a cell during the cell division cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Proteins / metabolism
  • Carrier Proteins / metabolism
  • Cell Division / physiology
  • Cell Nucleolus / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA Topoisomerases, Type II / metabolism
  • DNA-Binding Proteins
  • Female
  • Humans
  • Ki-67 Antigen / metabolism*
  • Ki-67 Antigen / physiology
  • Microscopy, Confocal
  • Nuclear Proteins / metabolism
  • Phosphoproteins / metabolism
  • Protein Inhibitors of Activated STAT
  • Proteins*
  • RNA Helicases / metabolism
  • RNA-Binding Proteins / metabolism
  • Retinoblastoma-Like Protein p130
  • Ribosomes / metabolism
  • Small Ubiquitin-Related Modifier Proteins*
  • Tumor Cells, Cultured
  • tRNA Methyltransferases

Substances

  • Blood Proteins
  • Carrier Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • Nuclear Proteins
  • PIAS1 protein, human
  • Phosphoproteins
  • Protein Inhibitors of Activated STAT
  • Proteins
  • RNA-Binding Proteins
  • Retinoblastoma-Like Protein p130
  • Small Ubiquitin-Related Modifier Proteins
  • fibrillarin
  • nucleolin
  • NOP2 protein, human
  • tRNA Methyltransferases
  • RNA Helicases
  • DNA Topoisomerases, Type II