Centromere and kinetochore proteins play a critical role in centromere structure, kinetochore formation, and sister chromatid separation. The protein encoded by this gene colocalizes with inner kinetochore plate proteins CENP-A and CENP-C in both interphase and metaphase. CENP-H is required for the localisation of CENP-C, but not CENP-A, to the centromere. However, it may be involved in the incorporation of newly synthesised CENP-A into centromeres via its interaction with the CENP-A/CENP-HI complex.[4] CENP-H localizes outside of centromeric heterochromatin, where CENP-B is localized, and inside the kinetochore corona, where CENP-E is localized during prometaphase. It is thought that this protein can bind to itself, as well as to CENP-A, CENP-B or CENP-C. Multimers of the protein localize constitutively to the inner kinetochore plate and play an important role in the organization and function of the active centromere-kinetochore complex.[5] CENP-H contains a coiled-coilstructure and a nuclear localisation signal.[5]
Studies show that CENP-H may be associated with certain humancancers.[6][7]
CENP-H shows sequence similarity to the Schizosaccharomyces pombe kinetochore protein Fta3 which is a subunit of the Sim4 complex. This complex is required for loading the DASH complex onto the kinetochore via interaction with dad1. Fta2, Fta3 and Fta4 associate with the central core and inner repeat region of the centromere.[8]
Other Protein Interactions
CENPH has also been shown to interact with KIAA0090.[9] The significance of this interaction is unclear.
References
↑Sugata N, Li S, Earnshaw WC, Yen TJ, Yoda K, Masumoto H, Munekata E, Warburton PE, Todokoro K (Jan 2001). "Human CENP-H multimers colocalize with CENP-A and CENP-C at active centromere--kinetochore complexes". Hum Mol Genet. 9 (19): 2919–26. doi:10.1093/hmg/9.19.2919. PMID11092768.
↑Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M (Nov 2004). "A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1". Nat Cell Biol. 6 (11): 1135–41. doi:10.1038/ncb1187. PMID15502821.
↑ 5.05.1Sugata N, Munekata E, Todokoro K (September 1999). "Characterization of a novel kinetochore protein, CENP-H". J. Biol. Chem. 274 (39): 27343–6. doi:10.1074/jbc.274.39.27343. PMID10488063.
↑Liao WT, Song LB, Zhang HZ, Zhang X, Zhang L, Liu WL, Feng Y, Guo BH, Mai HQ, Cao SM, Li MZ, Qin HD, Zeng YX, Zeng MS (January 2007). "Centromere protein H is a novel prognostic marker for nasopharyngeal carcinoma progression and overall patient survival". Clin. Cancer Res. 13 (2 Pt 1): 508–14. doi:10.1158/1078-0432.CCR-06-1512. PMID17255272.
Obuse C, Yang H, Nozaki N, et al. (2004). "Proteomics analysis of the centromere complex from HeLa interphase cells: UV-damaged DNA binding protein 1 (DDB-1) is a component of the CEN-complex, while BMI-1 is transiently co-localized with the centromeric region in interphase". Genes Cells. 9 (2): 105–20. doi:10.1111/j.1365-2443.2004.00705.x. PMID15009096.
Tomonaga T, Matsushita K, Ishibashi M, et al. (2005). "Centromere protein H is up-regulated in primary human colorectal cancer and its overexpression induces aneuploidy". Cancer Res. 65 (11): 4683–9. doi:10.1158/0008-5472.CAN-04-3613. PMID15930286.
Foltz DR, Jansen LE, Black BE, et al. (2006). "The human CENP-A centromeric nucleosome-associated complex". Nat. Cell Biol. 8 (5): 458–69. doi:10.1038/ncb1397. PMID16622419.
Okada M, Cheeseman IM, Hori T, et al. (2006). "The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres". Nat. Cell Biol. 8 (5): 446–57. doi:10.1038/ncb1396. PMID16622420.
Izuta H, Ikeno M, Suzuki N, et al. (2006). "Comprehensive analysis of the ICEN (Interphase Centromere Complex) components enriched in the CENP-A chromatin of human cells". Genes Cells. 11 (6): 673–84. doi:10.1111/j.1365-2443.2006.00969.x. PMID16716197.
Orthaus S, Ohndorf S, Diekmann S (2006). "RNAi knockdown of human kinetochore protein CENP-H". Biochem. Biophys. Res. Commun. 348 (1): 36–46. doi:10.1016/j.bbrc.2006.06.187. PMID16875666.
Liao WT, Song LB, Zhang HZ, et al. (2007). "Centromere protein H is a novel prognostic marker for nasopharyngeal carcinoma progression and overall patient survival". Clin. Cancer Res. 13 (2 Pt 1): 508–14. doi:10.1158/1078-0432.CCR-06-1512. PMID17255272.
