Recombinant Human Proliferation marker protein Ki-67 (MKI67), partial

Function

Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636)

Subcellular Location

Chromosome; Nucleus; Nucleus, nucleolus

Subunit

Interacts with KIF15 (PubMed:10878014). Interacts (via the FHA domain) with NIFK (PubMed:11342549, PubMed:14659764, PubMed:16244663). Interacts with PPP1CC (PubMed:24867636, PubMed:25012651). Component of a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5; the complex is formed as a result of interactions between components of a nuclear receptor-mediated transcription complex and a histone methylation complex (PubMed:19131338). Interacts with ZNF335 (PubMed:19131338, PubMed:23178126)

• Schlueter C. et al. The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins. — J. Cell Biol. (1993)
• Deloukas P. et al. The DNA sequence and comparative analysis of human chromosome 10. — Nature (2004)
• Gerdes J. et al. Sequence of the human Ki-67 protein gene 5' and promoter region. (MAR-)
• Gerdes J. et al. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. — Int. J. Cancer (1983)
• Gerdes J. et al. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. — J. Immunol. (1984)
• Verheijen R. et al. Ki-67 detects a nuclear matrix-associated proliferation-related antigen. I. Intracellular localization during interphase. — J. Cell Sci. (1989)
• Kill I.R. et al. Localisation of the Ki-67 antigen within the nucleolus. Evidence for a fibrillarin-deficient region of the dense fibrillar component. — J. Cell Sci. (1996)
• Bridger J.M. et al. Association of pKi-67 with satellite DNA of the human genome in early G1 cells. — Chromosome Res. (1998)