Ki-67: more than a proliferation marker

Chromosoma. 2018 Jun;127(2):175-186. doi: 10.1007/s00412-018-0659-8. Epub 2018 Jan 10.


Ki-67 protein has been widely used as a proliferation marker for human tumor cells for decades. In recent studies, multiple molecular functions of this large protein have become better understood. Ki-67 has roles in both interphase and mitotic cells, and its cellular distribution dramatically changes during cell cycle progression. These localizations correlate with distinct functions. For example, during interphase, Ki-67 is required for normal cellular distribution of heterochromatin antigens and for the nucleolar association of heterochromatin. During mitosis, Ki-67 is essential for formation of the perichromosomal layer (PCL), a ribonucleoprotein sheath coating the condensed chromosomes. In this structure, Ki-67 acts to prevent aggregation of mitotic chromosomes. Here, we present an overview of functional roles of Ki-67 across the cell cycle and also describe recent experiments that clarify its role in regulating cell cycle progression in human cells.

Keywords: Cell cycle; Heterochromatin; Ki-67; Perichromosomal layer.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amino Acid Sequence
  • Cell Line, Tumor
  • Cell Nucleolus / metabolism*
  • Cell Nucleolus / ultrastructure
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Gene Expression Regulation
  • Heterochromatin / metabolism*
  • Heterochromatin / ultrastructure
  • Humans
  • Interphase
  • Ki-67 Antigen / genetics*
  • Ki-67 Antigen / metabolism
  • Mitosis*
  • Protein Domains
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism
  • Ribonucleoproteins / chemistry
  • Ribonucleoproteins / genetics*
  • Ribonucleoproteins / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism


  • Cyclin-Dependent Kinase Inhibitor p21
  • Heterochromatin
  • Ki-67 Antigen
  • Protein Isoforms
  • Retinoblastoma Protein
  • Ribonucleoproteins
  • Tumor Suppressor Protein p53