Ki-67 (protein)

Marker of proliferation Ki-67
PDB rendering based on 1r21.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1R21​, 2AFF​
Identifiers
Symbols	MKI67 ; KIA; MIB-; MIB-1; PPP1R105
External IDs	OMIM: 176741 MGI: 106035 HomoloGene: 1814 GeneCards: MKI67 Gene
Gene ontology Molecular function • protein binding • ATP binding • protein C-terminus binding • poly(A) RNA binding Cellular component • chromosome, centromeric region • condensed chromosome • nucleus • nucleolus • cytoplasm • membrane Biological process • DNA metabolic process • meiotic nuclear division • cell proliferation • response to organic cyclic compound • hyaluronan metabolic process • organ regeneration • cellular response to heat Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4288	17345
Ensembl	ENSG00000148773	ENSMUSG00000031004
UniProt	P46013	E9PVX6
RefSeq (mRNA)	NM_001145966	NM_001081117
RefSeq (protein)	NP_001139438	NP_001074586
Location (UCSC)	Chr 10: 128.1 – 128.13 Mb	Chr 7: 135.69 – 135.72 Mb
PubMed search

Antigen KI-67 also known as Ki-67 or MKI67 is a protein that in humans is encoded by the MKI67 gene (antigen identified by monoclonal antibody Ki-67).^[1][2][3]

Function

Antigen KI-67 is a nuclear protein that is associated with and may be necessary for cellular proliferation. Furthermore, it is associated with ribosomal RNA transcription.^[3] Inactivation of antigen KI-67 leads to inhibition of ribosomal RNA synthesis.^[4]

Use as cell marker

Ki-67 immunostaining of a brain tumour with a high proliferative rate.

The Ki-67 protein (also known as MKI67) is a cellular marker for proliferation.^[5] It is strictly associated with cell proliferation. During interphase, the Ki-67 antigen can be exclusively detected within the cell nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. Ki-67 protein is present during all active phases of the cell cycle (G₁, S, G₂, and mitosis), but is absent from resting cells (G₀).

Antibody labeling

Ki-67 is an excellent marker to determine the growth fraction of a given cell population. The fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) is often correlated with the clinical course of cancer. The best-studied examples in this context are carcinomas of the prostate, brain and the breast and nephroblastoma. For these types of tumors, the prognostic value for survival and tumor recurrence have repeatedly been proven in uni- and multivariate analysis.

MIB-1

Ki-67 and MIB-1 monoclonal antibodies are directed against different epitopes of the same proliferation-related antigen. Ki-67 and MIB1 may be used on fixed sections.^[6] MIB-1 is used in clinical applications to determine the Ki-67 labelling index. One of its primary advantages over the original Ki-67 antibody (and the reason why it has essentially supplanted the original antibody for clinical use) is that it can be used on formalin-fixed paraffin-embedded sections, after heat-mediated antigen retrieval (see next section below).

Original Ki-67 antibody

The Ki-67 protein was originally defined by the prototype monoclonal antibody Ki-67,^[7] which was generated by immunizing mice with nuclei of the Hodgkin lymphoma cell line L428. The name is derived from the city of origin (Kiel, Germany) and the number of the original clone in the 96-well plate.

Interactions

Ki-67 (protein) has been shown to interact with CBX3.^[8]

See also

• PCNA - Proliferating Cell Nuclear Antigen, expressed during the DNA synthesis.

Additional images

• 

  Immunofluorescent antibody staining against neurofilament (green) and Ki-67 (red) in a mouse embryo 12.5 days after fertilization. The proliferating cells are in the ventricular zone in the neural tube and therefore colored red.

References

1. "Entrez Gene: Antigen identified by monoclonal antibody Ki-67".
2. Schonk DM, Kuijpers HJ, van Drunen E, van Dalen CH, Geurts van Kessel AH, Verheijen R, Ramaekers FC (October 1989). "Assignment of the gene(s) involved in the expression of the proliferation-related Ki-67 antigen to human chromosome 10". Hum. Genet. 83 (3): 297–9. doi:10.1007/BF00285178. PMID 2571566.
3. Bullwinkel J, Baron-Lühr B, Lüdemann A, Wohlenberg C, Gerdes J, Scholzen T (March 2006). "Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells". J. Cell. Physiol. 206 (3): 624–35. doi:10.1002/jcp.20494. PMID 16206250.
4. Rahmanzadeh R, Hüttmann G, Gerdes J, Scholzen T (June 2007). "Chromophore-assisted light inactivation of pKi-67 leads to inhibition of ribosomal RNA synthesis". Cell Prolif. 40 (3): 422–30. doi:10.1111/j.1365-2184.2007.00433.x. PMID 17531085.
5. Scholzen T, Gerdes J (March 2000). "The Ki-67 protein: from the known and the unknown". J. Cell. Physiol. 182 (3): 311–22. doi:10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9. PMID 10653597.
6. Bánkfalvi A (November 2000). "Comparative methodological analysis of erbB-2/HER-2 gene dosage, chromosomal copy number and protein overexpression in breast carcinoma tissues for diagnostic use.". Histopathology 37 (5): 411–9. doi:10.1046/j.1365-2559.2000.00984.x. PMID 11119122.
7. Gerdes J, Schwab U, Lemke H, Stein H (1983). "Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation". Int. J. Cancer 31 (1): 13–20. doi:10.1002/ijc.2910310104. PMID 6339421.
8. Kametaka, Ai; Takagi Masatoshi; Hayakawa Tomohiro; Haraguchi Tokuko; Hiraoka Yasushi; Yoneda Yoshihiro (Dec 2002). "Interaction of the chromatin compaction-inducing domain (LR domain) of Ki-67 antigen with HP1 proteins". Genes Cells (England) 7 (12): 1231–42. doi:10.1046/j.1365-2443.2002.00596.x. ISSN 1356-9597. PMID 12485163.

External links

• Ki-67 Antigen at the US National Library of Medicine Medical Subject Headings (MeSH)
• http://www.pathologyoutlines.com/topic/stainski67.html