INCENP explained

Symbol:	INCENP_N
Chromosome passenger complex (CPC) protein INCENP N terminal
Pfam:	PF12178
Interpro:	IPR022006

Symbol:	INCENP_ARK-bind
Inner centromere protein, ARK binding region
Pfam:	PF03941
Interpro:	IPR005635

Inner centromere protein is a protein that in humans is encoded by the INCENP gene.^{[1] [2] [3]} It is a regulatory protein in the chromosome passenger complex (CPC). It is involved in regulation of the catalytic proteins Aurora B and Aurora C.^{[4] [5] [6]} It acts in association with two other proteins - Survivin and Borealin. These proteins form a tight three-helical bundle. The N-terminal domain of INCENP is the domain involved in formation of this three-helical bundle while its C-terminal domain is responsible for the interaction with Aurora B.^{[7] [6]}

In mammalian cells, two broad groups of centromere-interacting proteins have been described: constitutively binding centromere proteins and 'passenger' (or transiently interacting) proteins.^[8] The constitutive proteins include CENPA (centromere protein A), CENPB, CENPC1, and CENPD.

The term 'passenger proteins' encompasses a broad collection of proteins that localize to the centromere during specific stages of the cell cycle.^[9] These include CENPE; MCAK; KID; cytoplasmic dynein (e.g., DYNC1H1); CliPs (e.g. CLIP1); and CENPF/mitosin (CENPF). The inner centromere proteins (INCENPs), the initial members of the passenger protein group, display a broad localization along chromosomes in the early stages of mitosis but gradually become concentrated at centromeres as the cell cycle progresses into mid-metaphase. During telophase, the proteins are located within the midbody in the intercellular bridge, where they are discarded after cytokinesis.^{[3] [10]}

Interactions

INCENP has been shown to interact with H2AFZ,^[11] Survivin^[12] and CDCA8.^[13] The ARK binding region has been found to be necessary and sufficient for binding to aurora-related kinase. This interaction has been implicated in the coordination of chromosome segregation with cell division in yeast.^[14]

Further reading

• Ainsztein AM, Kandels-Lewis SE, Mackay AM, Earnshaw WC . INCENP centromere and spindle targeting: identification of essential conserved motifs and involvement of heterochromatin protein HP1. . J. Cell Biol. . 143 . 7 . 1763–74 . 1999 . 9864353 . 10.1083/jcb.143.7.1763 . 2175214 .
• Martineau-Thuillier S, Andreassen PR, Margolis RL . Colocalization of TD-60 and INCENP throughout G2 and mitosis: evidence for their possible interaction in signalling cytokinesis. . Chromosoma . 107 . 6–7 . 461–70 . 1999 . 9914378 . 10.1007/s004120050330 . 24935187 .
• Dias Neto E, Correa RG, Verjovski-Almeida S, etal . Shotgun sequencing of the human transcriptome with ORF expressed sequence tags. . Proc. Natl. Acad. Sci. U.S.A. . 97 . 7 . 3491–6 . 2000 . 10737800 . 10.1073/pnas.97.7.3491 . 16267 . 2000PNAS...97.3491D . free .
• Wheatley SP, Kandels-Lewis SE, Adams RR, etal . INCENP binds directly to tubulin and requires dynamic microtubules to target to the cleavage furrow. . Exp. Cell Res. . 262 . 2 . 122–7 . 2001 . 11139336 . 10.1006/excr.2000.5088 .
• Wheatley SP, Carvalho A, Vagnarelli P, Earnshaw WC . INCENP is required for proper targeting of Survivin to the centromeres and the anaphase spindle during mitosis. . Curr. Biol. . 11 . 11 . 886–90 . 2001 . 11516652 . 10.1016/S0960-9822(01)00238-X . free . 2001CBio...11..886W .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Parra MT, Viera A, Gómez R, etal . Dynamic relocalization of the chromosomal passenger complex proteins inner centromere protein (INCENP) and aurora-B kinase during male mouse meiosis. . J. Cell Sci. . 116 . Pt 6 . 961–74 . 2003 . 12584241 . 10.1242/jcs.00330 . free .
• Rangasamy D, Berven L, Ridgway P, Tremethick DJ . Pericentric heterochromatin becomes enriched with H2A.Z during early mammalian development. . EMBO J. . 22 . 7 . 1599–607 . 2003 . 12660166 . 10.1093/emboj/cdg160 . 152904 .
• Honda R, Körner R, Nigg EA . Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis. . Mol. Biol. Cell . 14 . 8 . 3325–41 . 2004 . 12925766 . 10.1091/mbc.E02-11-0769 . 181570 .
• Wheatley SP, Henzing AJ, Dodson H, etal . Aurora-B phosphorylation in vitro identifies a residue of survivin that is essential for its localization and binding to inner centromere protein (INCENP) in vivo. . J. Biol. Chem. . 279 . 7 . 5655–60 . 2004 . 14610074 . 10.1074/jbc.M311299200 . free .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Gassmann R, Carvalho A, Henzing AJ, etal . Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle. . J. Cell Biol. . 166 . 2 . 179–91 . 2004 . 15249581 . 10.1083/jcb.200404001 . 2172304 .
• Li X, Sakashita G, Matsuzaki H, etal . Direct association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C. . J. Biol. Chem. . 279 . 45 . 47201–11 . 2004 . 15316025 . 10.1074/jbc.M403029200 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Zhu C, Bossy-Wetzel E, Jiang W . Recruitment of MKLP1 to the spindle midzone/midbody by INCENP is essential for midbody formation and completion of cytokinesis in human cells. . Biochem. J. . 389 . Pt 2 . 373–81 . 2005 . 15796717 . 10.1042/BJ20050097 . 1175114 .
• Chen HL, Tang CJ, Chen CY, Tang TK . Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP complex and induces polyploidy. . J. Biomed. Sci. . 12 . 2 . 297–310 . 2005 . 15917996 . 10.1007/s11373-005-0980-0 .
• Vader G, Kauw JJ, Medema RH, Lens SM . Survivin mediates targeting of the chromosomal passenger complex to the centromere and midbody. . EMBO Rep. . 7 . 1 . 85–92 . 2006 . 16239925 . 10.1038/sj.embor.7400562 . 1369225 .
• Goto H, Kiyono T, Tomono Y, etal . Complex formation of Plk1 and INCENP required for metaphase-anaphase transition. . Nat. Cell Biol. . 8 . 2 . 180–7 . 2006 . 16378098 . 10.1038/ncb1350 . 11583385 .

Notes and References

1. Earnshaw WC, Cooke CA . Analysis of the distribution of the INCENPs throughout mitosis reveals the existence of a pathway of structural changes in the chromosomes during metaphase and early events in cleavage furrow formation . J Cell Sci . 98 . 4. 443–61 . Sep 1991 . 10.1242/jcs.98.4.443 . 1860899 .
2. Adams RR, Eckley DM, Vagnarelli P, Wheatley SP, Gerloff DL, Mackay AM, Svingen PA, Kaufmann SH, Earnshaw WC . Human INCENP colocalizes with the Aurora-B/AIRK2 kinase on chromosomes and is overexpressed in tumour cells . Chromosoma . 110 . 2 . 65–74 . Jul 2001 . 11453556 . 10.1007/s004120100130 . 13778759 .
3. Web site: Entrez Gene: INCENP inner centromere protein antigens 135/155kDa.
4. Sasai . Kaori . Katayama . Hiroshi . Hawke . David H . Sen . Subrata . 2016-01-01 . Aurora-C Interactions with Survivin and INCENP Reveal Shared and Distinct Features Compared with Aurora-B Chromosome Passenger Protein Complex . PLOS ONE . 11 . 6 . e0157305 . 10.1371/journal.pone.0157305 . 1932-6203 . 4917241 . 27332895 . 2016PLoSO..1157305S . free .
5. Li . Xiangyu . Sakashita . Gyosuke . Matsuzaki . Hideki . Sugimoto . Kenji . Kimura . Keiji . Hanaoka . Fumio . Taniguchi . Hisaaki . Furukawa . Koichi . Urano . Takeshi . 2004-11-01 . Direct association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C . The Journal of Biological Chemistry . 279 . 45 . 47201–47211 . 10.1074/jbc.m403029200 . 1083-351X . 15316025 . free .
6. Honda . Reiko . Körner . Roman . Nigg . Erich A . 2003-08-01 . Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis . Molecular Biology of the Cell . 14 . 8 . 3325–3341 . 10.1091/mbc.e02-11-0769 . 1939-4586 . 12925766. 181570 .
7. Jeyaprakash . A. Arockia . Klein . Ulf R. . Lindner . Doris . Ebert . Judith . Nigg . Erich A. . Conti . Elena . 2007-10-19 . Structure of a Survivin–Borealin–INCENP Core Complex Reveals How Chromosomal Passengers Travel Together . Cell . en . 131 . 2 . 271–285 . 10.1016/j.cell.2007.07.045 . 17956729 . 15199822 . 0092-8674. free .
8. Book: Choo, K. H. Andy . The centromere . Oxford University Press . Oxford [Oxfordshire] . 1997 . 978-0-19-857780-5 . registration .
9. Earnshaw WC, Mackay AM . Role of nonhistone proteins in the chromosomal events of mitosis . FASEB J. . 8 . 12 . 947–56 . September 1994 . 8088460 . 10.1096/fasebj.8.12.8088460. free . 14062246 .
10. Cutts SM, Fowler KJ, Kile BT, Hii LL, O'Dowd RA, Hudson DF, Saffery R, Kalitsis P, Earle E, Choo KH . Defective chromosome segregation, microtubule bundling and nuclear bridging in inner centromere protein gene (Incenp)-disrupted mice . Hum. Mol. Genet. . 8 . 7 . 1145–55 . July 1999 . 10369859 . 10.1093/hmg/8.7.1145. free .
11. Rangasamy D, Berven L, Ridgway P, Tremethick DJ . Pericentric heterochromatin becomes enriched with H2A.Z during early mammalian development . EMBO J. . 22 . 7 . 1599–607 . April 2003 . 12660166 . 152904 . 10.1093/emboj/cdg160 .
12. Wheatley SP, Carvalho A, Vagnarelli P, Earnshaw WC . INCENP is required for proper targeting of Survivin to the centromeres and the anaphase spindle during mitosis . Curr. Biol. . 11 . 11 . 886–90 . June 2001 . 11516652 . 10.1016/S0960-9822(01)00238-X. free . 2001CBio...11..886W .
13. Gassmann R, Carvalho A, Henzing AJ, Ruchaud S, Hudson DF, Honda R, Nigg EA, Gerloff DL, Earnshaw WC . Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle . J. Cell Biol. . 166 . 2 . 179–91 . July 2004 . 15249581 . 2172304 . 10.1083/jcb.200404001 .
14. Leverson JD, Huang HK, Forsburg SL, Hunter T . The Schizosaccharomyces pombe aurora-related kinase Ark1 interacts with the inner centromere protein Pic1 and mediates chromosome segregation and cytokinesis . Mol. Biol. Cell . 13 . 4 . 1132–43 . April 2002 . 11950927 . 102257 . 10.1091/mbc.01-07-0330 .