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Gene Review

INCENP  -  inner centromere protein antigens 135/155kDa

Homo sapiens

Synonyms: FLJ31633, Inner centromere protein
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Disease relevance of INCENP

  • By using a complex of proteins expressed in baculovirus, immunoblot analysis demonstrated that the INCENP protein is a major autoantigen in this patient with GLPL syndrome [1].
  • In carcinomas, Incenp mRNA correlated with T category (p = 0.0149), and Survivin (p = 0.0382) and Cyclin-D1 (p = 0.0185) were associated with tumour differentiation [2].

High impact information on INCENP

  • Here we report the identification of Dasra A and Dasra B, two new components of the vertebrate chromosomal passenger complex containing Incenp, Survivin, and the kinase Aurora B, and demonstrate that this complex is required for chromatin-induced microtubule stabilization and spindle formation [3].
  • Phosphorylation of two serines in the carboxyl terminus of INCENP generates the fully active kinase [4].
  • This phenotype is rescued by the exogenous expression of INCENP wild type and INCENP mutated at Thr 59 to Ala (T59A), but not at Thr 388 to Ala (T388A) [5].
  • The replacement of endogenous INCENP with T388A resulted in the delay of progression from metaphase to anaphase [5].
  • PIASy-dependent SUMO-2-conjugated species were highly concentrated on the inner centromere, and inhibition of PIASy blocked anaphase sister chromatid segregation in egg extracts [6].

Biological context of INCENP

  • INCENP centromere and spindle targeting: identification of essential conserved motifs and involvement of heterochromatin protein HP1 [7].
  • To begin to understand the mechanisms of INCENP function in mitosis, we have performed a yeast two-hybrid screen for interacting proteins [7].
  • Surprisingly, this interaction does not appear to be involved in targeting INCENP to the centromeric heterochromatin, but may instead have a role in its transfer from the chromosomes to the anaphase spindle [7].
  • Furthermore, Aurora-C co-expressed with INCENP elicits the phosphorylation of endogenous histone H3 in mammalian cells, even though this phosphorylation is not sufficient to establish chromosome condensation in interphase cells [8].
  • A nonphosphorylatable mutant (TSS893-895AAA) was a poor activator of Aurora B, demonstrating that INCENP phosphorylation is important for kinase activation [9].

Anatomical context of INCENP


Associations of INCENP with chemical compounds


Physical interactions of INCENP


Enzymatic interactions of INCENP


Regulatory relationships of INCENP

  • We show that INCENP binds and activates Aurora-C in vivo and in vitro [8].
  • Using recombinant proteins, we found that Aurora B kinase activity was stimulated by INCENP and that the C-terminal region of INCENP was sufficient for activation [9].

Other interactions of INCENP


Analytical, diagnostic and therapeutic context of INCENP


  1. Autoantibodies against the chromosomal passenger protein INCENP found in a patient with Graham Little-Piccardi-Lassueur syndrome. Rodríguez-Bayona, B., Ruchaud, S., Rodríguez, C., Linares, M., Astola, A., Ortiz, M., Earnshaw, W.C., Valdivia, M.M. Journal of autoimmune diseases (2007) [Pubmed]
  2. Centrosome-, chromosomal-passenger- and cell-cycle-associated mRNAs are differentially regulated in the development of sporadic colorectal cancer. Gerlach, U., Kayser, G., Walch, A., Hopt, U., Schulte-Mönting, J., Werner, M., Lassmann, S. J. Pathol. (2006) [Pubmed]
  3. The chromosomal passenger complex is required for chromatin-induced microtubule stabilization and spindle assembly. Sampath, S.C., Ohi, R., Leismann, O., Salic, A., Pozniakovski, A., Funabiki, H. Cell (2004) [Pubmed]
  4. Mechanism of Aurora B activation by INCENP and inhibition by hesperadin. Sessa, F., Mapelli, M., Ciferri, C., Tarricone, C., Areces, L.B., Schneider, T.R., Stukenberg, P.T., Musacchio, A. Mol. Cell (2005) [Pubmed]
  5. Complex formation of Plk1 and INCENP required for metaphase-anaphase transition. Goto, H., Kiyono, T., Tomono, Y., Kawajiri, A., Urano, T., Furukawa, K., Nigg, E.A., Inagaki, M. Nat. Cell Biol. (2006) [Pubmed]
  6. PIASy mediates SUMO-2 conjugation of Topoisomerase-II on mitotic chromosomes. Azuma, Y., Arnaoutov, A., Anan, T., Dasso, M. EMBO J. (2005) [Pubmed]
  7. INCENP centromere and spindle targeting: identification of essential conserved motifs and involvement of heterochromatin protein HP1. Ainsztein, A.M., Kandels-Lewis, S.E., Mackay, A.M., Earnshaw, W.C. J. Cell Biol. (1998) [Pubmed]
  8. Direct association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C. Li, X., Sakashita, G., Matsuzaki, H., Sugimoto, K., Kimura, K., Hanaoka, F., Taniguchi, H., Furukawa, K., Urano, T. J. Biol. Chem. (2004) [Pubmed]
  9. Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis. Honda, R., Körner, R., Nigg, E.A. Mol. Biol. Cell (2003) [Pubmed]
  10. INCENP is required for proper targeting of Survivin to the centromeres and the anaphase spindle during mitosis. Wheatley, S.P., Carvalho, A., Vagnarelli, P., Earnshaw, W.C. Curr. Biol. (2001) [Pubmed]
  11. INCENP binds directly to tubulin and requires dynamic microtubules to target to the cleavage furrow. Wheatley, S.P., Kandels-Lewis, S.E., Adams, R.R., Ainsztein, A.M., Earnshaw, W.C. Exp. Cell Res. (2001) [Pubmed]
  12. Neocentromere formation in a stable ring 1p32-p36.1 chromosome. Slater, H.R., Nouri, S., Earle, E., Lo, A.W., Hale, L.G., Choo, K.H. J. Med. Genet. (1999) [Pubmed]
  13. Cleavage furrows formed between centrosomes lacking an intervening spindle and chromosomes contain microtubule bundles, INCENP, and CHO1 but not CENP-E. Savoian, M.S., Earnshaw, W.C., Khodjakov, A., Rieder, C.L. Mol. Biol. Cell (1999) [Pubmed]
  14. Incomplete sister chromatid separation of long chromosome arms. Rens, W., Torosantucci, L., Degrassi, F., Ferguson-Smith, M.A. Chromosoma (2006) [Pubmed]
  15. 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. Wheatley, S.P., Henzing, A.J., Dodson, H., Khaled, W., Earnshaw, W.C. J. Biol. Chem. (2004) [Pubmed]
  16. INCENP binds the Aurora-related kinase AIRK2 and is required to target it to chromosomes, the central spindle and cleavage furrow. Adams, R.R., Wheatley, S.P., Gouldsworthy, A.M., Kandels-Lewis, S.E., Carmena, M., Smythe, C., Gerloff, D.L., Earnshaw, W.C. Curr. Biol. (2000) [Pubmed]
  17. Autophosphorylation of a newly identified site of Aurora-B is indispensable for cytokinesis. Yasui, Y., Urano, T., Kawajiri, A., Nagata, K., Tatsuka, M., Saya, H., Furukawa, K., Takahashi, T., Izawa, I., Inagaki, M. J. Biol. Chem. (2004) [Pubmed]
  18. Recruitment of MKLP1 to the spindle midzone/midbody by INCENP is essential for midbody formation and completion of cytokinesis in human cells. Zhu, C., Bossy-Wetzel, E., Jiang, W. Biochem. J. (2005) [Pubmed]
  19. CENP-A is phosphorylated by Aurora B kinase and plays an unexpected role in completion of cytokinesis. Zeitlin, S.G., Shelby, R.D., Sullivan, K.F. J. Cell Biol. (2001) [Pubmed]
  20. EVI5 protein associates with the INCENP-aurora B kinase-survivin chromosomal passenger complex and is involved in the completion of cytokinesis. Faitar, S.L., Sossey-Alaoui, K., Ranalli, T.A., Cowell, J.K. Exp. Cell Res. (2006) [Pubmed]
  21. Colocalization of TD-60 and INCENP throughout G2 and mitosis: evidence for their possible interaction in signalling cytokinesis. Martineau-Thuillier, S., Andreassen, P.R., Margolis, R.L. Chromosoma (1998) [Pubmed]
  22. Human INCENP colocalizes with the Aurora-B/AIRK2 kinase on chromosomes and is overexpressed in tumour cells. Adams, R.R., Eckley, D.M., Vagnarelli, P., Wheatley, S.P., Gerloff, D.L., Mackay, A.M., Svingen, P.A., Kaufmann, S.H., Earnshaw, W.C. Chromosoma (2001) [Pubmed]
  23. Recapitulation of the Roberts syndrome cellular phenotype by inhibition of INCENP, ZWINT-1 and ZW10 genes. Musio, A., Mariani, T., Montagna, C., Zambroni, D., Ascoli, C., Ried, T., Vezzoni, P. Gene (2004) [Pubmed]
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