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Gene Review

CENPF  -  centromere protein F, 350/400kDa

Homo sapiens

Synonyms: AH antigen, CENF, CENP-F, Centromere protein F, Kinetochore protein CENPF, ...
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Disease relevance of CENPF


High impact information on CENPF


Biological context of CENPF


Anatomical context of CENPF


Associations of CENPF with chemical compounds

  • Studies of the centromere-associated protein mitosin revealed that treatment with lovastatin and paclitaxel resulted in increased mitosin levels and that lovastatin altered the association of mitosin with condensed chromosomes [14].
  • Using a new monoclonal antibody (14C10), this pilot study evaluated mitosin expression by IHC in a series of 386 node-negative, formalin-fixed, archival breast cancers and correlated the results with several prognostic factors and clinical outcome (median follow-up, 78 months; range 3-214 months) [5].

Physical interactions of CENPF

  • The C-terminal portion of mitosin between residues 2488 and 3113 bound to ATF4 through two distinct domains, one of which was a leucine zipper motif [11].

Other interactions of CENPF

  • The CENPF gene, which encodes a structural protein of the kinetochore, maps to chromosome 1q32-->q41 within close proximity to the genetic locus that is linked to Van der Woude syndrome [10].
  • The higher proliferation indices were obtained with mitosin and PCNA and the lower ones with TopoIIalpha [3].
  • In multivariate analysis, the labeling indices of mitosin (p = 0.035) and Ki-67 (p = 0.032), along with tumor size, were shown to provide independent prognostic information, beyond that obtained by standard clinical and pathological parameters [3].
  • Mitosin/CENP-F is a large nuclear/kinetochore protein containing multiple leucine zipper motifs potentially for protein interactions [15].
  • Nuclear grade, mitotic activity, and biomarker profile (Her2-neu and mitosin expression patterns) in pretreatment tumors were correlated with the postchemotherapy pathologic response [16].

Analytical, diagnostic and therapeutic context of CENPF

  • Univariate analysis disclosed mitosin LI (p = 0.033) along with the mitotic index (p = 0.024) and tumor size (p = 0.028) as significant predictors of shortened recurrence-free survival [3].
  • However, in a univariate cutpoint analysis of disease-free survival (DFS), patients with high levels of mitosin (>9% positive cells) had significantly worse DFS than did patients with lower levels (68% versus 84% at 5 years, respectively) [5].
  • Mitosin also was correlated significantly with CPR and NCR (P = 0.028) [16].
  • CONCLUSIONS: The current results indicate that tumor nuclear grade and tumor proliferative activity (mitotic activity and mitosin immunostaining) of pretreatment tumors in patients with breast carcinoma may serve as important indicators for the pathologic responsiveness of tumors to neoadjuvant, anthracycline-based chemotherapy [16].


  1. Nonrandom chromosomal imbalances in esophageal squamous cell carcinoma cell lines: possible involvement of the ATF3 and CENPF genes in the 1q32 amplicon. Pimkhaokham, A., Shimada, Y., Fukuda, Y., Kurihara, N., Imoto, I., Yang, Z.Q., Imamura, M., Nakamura, Y., Amagasa, T., Inazawa, J. Jpn. J. Cancer Res. (2000) [Pubmed]
  2. Characterization of a novel 350-kilodalton nuclear phosphoprotein that is specifically involved in mitotic-phase progression. Zhu, X., Mancini, M.A., Chang, K.H., Liu, C.Y., Chen, C.F., Shan, B., Jones, D., Yang-Feng, T.L., Lee, W.H. Mol. Cell. Biol. (1995) [Pubmed]
  3. Mitosin, a novel marker of cell proliferation and early recurrence in intracranial meningiomas. Konstantinidou, A.E., Korkolopoulou, P., Kavantzas, N., Mahera, H., Thymara, I., Kotsiakis, X., Perdiki, M., Patsouris, E., Davaris, P. Histol. Histopathol. (2003) [Pubmed]
  4. Human melanoma antigen AH is an autoantigenic ganglioside related to GD2. Watanabe, T., Pukel, C.S., Takeyama, H., Lloyd, K.O., Shiku, H., Li, L.T., Travassos, L.R., Oettgen, H.F., Old, L.J. J. Exp. Med. (1982) [Pubmed]
  5. Mitosin (a new proliferation marker) correlates with clinical outcome in node-negative breast cancer. Clark, G.M., Allred, D.C., Hilsenbeck, S.G., Chamness, G.C., Osborne, C.K., Jones, D., Lee, W.H. Cancer Res. (1997) [Pubmed]
  6. The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4. Sayer, J.A., Otto, E.A., O'Toole, J.F., Nurnberg, G., Kennedy, M.A., Becker, C., Hennies, H.C., Helou, J., Attanasio, M., Fausett, B.V., Utsch, B., Khanna, H., Liu, Y., Drummond, I., Kawakami, I., Kusakabe, T., Tsuda, M., Ma, L., Lee, H., Larson, R.G., Allen, S.J., Wilkinson, C.J., Nigg, E.A., Shou, C., Lillo, C., Williams, D.S., Hoppe, B., Kemper, M.J., Neuhaus, T., Parisi, M.A., Glass, I.A., Petry, M., Kispert, A., Gloy, J., Ganner, A., Walz, G., Zhu, X., Goldman, D., Nurnberg, P., Swaroop, A., Leroux, M.R., Hildebrandt, F. Nat. Genet. (2006) [Pubmed]
  7. Unstable microtubule capture at kinetochores depleted of the centromere-associated protein CENP-F. Bomont, P., Maddox, P., Shah, J.V., Desai, A.B., Cleveland, D.W. EMBO J. (2005) [Pubmed]
  8. CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis. Liao, H., Winkfein, R.J., Mack, G., Rattner, J.B., Yen, T.J. J. Cell Biol. (1995) [Pubmed]
  9. Silencing mitosin induces misaligned chromosomes, premature chromosome decondensation before anaphase onset, and mitotic cell death. Yang, Z., Guo, J., Chen, Q., Ding, C., Du, J., Zhu, X. Mol. Cell. Biol. (2005) [Pubmed]
  10. Chromosomal localization of the genes encoding the kinetochore proteins CENPE and CENPF to human chromosomes 4q24-->q25 and 1q32-->q41, respectively, by fluorescence in situ hybridization. Testa, J.R., Zhou, J.Y., Bell, D.W., Yen, T.J. Genomics (1994) [Pubmed]
  11. Mitosin/CENP-F as a negative regulator of activating transcription factor-4. Zhou, X., Wang, R., Fan, L., Li, Y., Ma, L., Yang, Z., Yu, W., Jing, N., Zhu, X. J. Biol. Chem. (2005) [Pubmed]
  12. Structural requirements and dynamics of mitosin-kinetochore interaction in M phase. Zhu, X. Mol. Cell. Biol. (1999) [Pubmed]
  13. The C terminus of mitosin is essential for its nuclear localization, centromere/kinetochore targeting, and dimerization. Zhu, X., Chang, K.H., He, D., Mancini, M.A., Brinkley, W.R., Lee, W.H. J. Biol. Chem. (1995) [Pubmed]
  14. Synergistic interaction of lovastatin and paclitaxel in human cancer cells. Holstein, S.A., Hohl, R.J. Mol. Cancer Ther. (2001) [Pubmed]
  15. Mitosin/CENP-F in mitosis, transcriptional control, and differentiation. Ma, L., Zhao, X., Zhu, X. J. Biomed. Sci. (2006) [Pubmed]
  16. Assessment of histologic features and expression of biomarkers in predicting pathologic response to anthracycline-based neoadjuvant chemotherapy in patients with breast carcinoma. Wang, J., Buchholz, T.A., Middleton, L.P., Allred, D.C., Tucker, S.L., Kuerer, H.M., Esteva, F.J., Hortobagyi, G.N., Sahin, A.A. Cancer (2002) [Pubmed]
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