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Gene Review:

CENPC - centromere protein C

Homo sapiens

Synonyms: CENP-C, CENP-C 1, CENPC1, Centromere autoantigen C, Centromere protein C, ...

Chung, T.L. et al., Pluta, A.F. et al., Saitoh, H. et al., Sugimoto, K. et al., Liu, S.T. et al., et al.

Everett, Earnshaw, Findlay, Lomonte, Pluta, Earnshaw, Goldberg, Everett, Earnshaw, Pluta, Sternsdorf, Ainsztein, Carmena, Ruchaud, Hsu, Orr, Pillemer, Casciola-Rosen, Baum, Rosen, Gelber, Fukagawa, Regnier, Ikemura, Xie, Heng, Fukagawa, Brown,

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Disease relevance of CENPC1

Centromere protein C is a target of autoantibodies in Sjögren's syndrome and is uniformly associated with antibodies to Ro and La [1].
We independently isolated a full-length cDNA encoding human CENP-C and expressed it as the polypeptide tagged with histidine oligomer in Escherichia coli [2].
Specific destruction of kinetochore protein CENP-C and disruption of cell division by herpes simplex virus immediate-early protein Vmw110 [3].
CONCLUSION: The results indicated the existence of different anti-CENP-C responses in rheumatic diseases and a possible correlation between antigenic regions and functional sites in the CENP-C antigen [4].
METHODS: A series of truncated peptides of human CENP-C were expressed in Escherichia coli and immunoblotting analysis was performed with 45 ACA positive sera obtained from patients with different types of autoimmune diseases [4].

High impact information on CENPC1

PTEN was found localized at centromeres and physically associated with CENP-C, an integral component of the kinetochore [5].
We have isolated and characterized a set of overlapping cDNA clones that encode the human centromere autoantigen centromere protein C (CENP-C) [6].
Localization of CENP-C by immunoelectron microscopy reveals that this protein is a component of the inner kinetochore plate [6].
CENP-C, an autoantigen in scleroderma, is a component of the human inner kinetochore plate [6].
Centromere protein (CENP)-A is at the top of a hierarchy that directs three major pathways, which are specified by CENP-C, -I, and Aurora B [7].

Biological context of CENPC1

Complementary EM studies found that the formation of kinetochore trilaminar plates depends on the CENP-I/NUF2 branch, whereas CENP-C and Aurora B affect the size, shape, and structural integrity of the plates [7].
A role in the control of chromosome dynamics was first suggested when SUMO was identified as high-copy suppressor of the centromere protein CENP-C mutants [8].
Double indirect immunofluorescence using monospecific antibodies demonstrated that a subset of CENP-C and UBF/NOR-90 is colocalized at nucleoli of interphase HeLa cells, suggesting that the in vitro interaction detected by affinity chromatography may reflect an interaction that occurs in vivo [9].
FISH mapping of centromere protein C (CENPC) on human chromosome 4q31-->q21 [10].
Overproduction of truncated CENP-B containing no CENP-C interaction domains caused abnormal duplication of CENP-C domains at G2 and cell cycle delay at metaphase [11].

Anatomical context of CENPC1

To further understand CENP-C function, we developed a method incorporating the hyper-recombinogenic chicken B lymphocyte cell line DT40 to create several temperature-sensitive CENP-C mutants in DT40 cells [12].
These observations are consistent with an involvement of CENP-C in kinetochore assembly, and suggest that CENP-C plays a critical role in both establishing and/or maintaining proper kinetochore size and stabilizing microtubule attachments [13].
In both fibroblast and lymphoblast cell lines containing the translocation, the X chromosome centromere consistently had a primary constriction and CENP-C immunofluorescence, and is therefore the active centromere [14].

Associations of CENPC1 with chemical compounds

We have used gene targeting in the DT40 cell line to create a cell line which expresses a fusion between CENP-C and a mouse steroid receptor and which behaves as a conditional loss of function mutant of CENP-C [15].

Other interactions of CENPC1

In vitro modification of human centromere protein CENP-C fragments by small ubiquitin-like modifier (SUMO) protein: definitive identification of the modification sites by tandem mass spectrometry analysis of the isopeptides [8].
CENP-C is a human kinetochore protein that was originally identified as a chromosomal autoantigen in patients with scleroderma spectrum disease [9].
Strong reduction of CENP-H resulted in a slightly reduced CENP-C level at the kinetochores and normal localisation of hBubR1, indicating a functional mitotic checkpoint at the hBubR1 protein level [16].
Caspase-mediated cleavage of CENP-C and INCENP results in their mislocalization and the subsequent mislocalization of Aurora B kinase [17].
In this paper we report that hDaxx and HP1 (which have been shown to interact with CENP-C and Sp100, respectively) are present in a proportion of both ND10 and interphase centromeres [18].

Analytical, diagnostic and therapeutic context of CENPC1

To begin to establish a comprehensive protein map of the human centromere, affinity chromatography was used to identify nuclear proteins that specifically interact with CENP-C [9].
To ascertain whether CENP-C can be sumoylated, tandem mass spectrometry (MS) based strategy was developed for high sensitivity identification and sequencing of sumoylated isopeptides present among in-gel-digested tryptic peptides of SDS-PAGE fractionated target proteins [8].
In addition, we used indirect immunofluorescence to demonstrate that these antibodies recognize centromeres of HeLa chromosomes in the expected pattern for CENP-C [6].
The biological significance of the interaction between CENP-C and HDaxx was confirmed by immunofluorescence colocalization of these two proteins at discrete spots in the nuclei of some interphase HeLa cells [19].
We performed a detailed molecular dissection of this domain to understand the mechanism by which CENP-C assembles at centromeres [20].

References

Centromere protein C is a target of autoantibodies in Sjögren's syndrome and is uniformly associated with antibodies to Ro and La. Pillemer, S.R., Casciola-Rosen, L., Baum, B.J., Rosen, A., Gelber, A.C. J. Rheumatol. (2004) [Pubmed]
Human centromere protein C (CENP-C) is a DNA-binding protein which possesses a novel DNA-binding motif. Sugimoto, K., Yata, H., Muro, Y., Himeno, M. J. Biochem. (1994) [Pubmed]
Specific destruction of kinetochore protein CENP-C and disruption of cell division by herpes simplex virus immediate-early protein Vmw110. Everett, R.D., Earnshaw, W.C., Findlay, J., Lomonte, P. EMBO J. (1999) [Pubmed]
Epitope mapping of human centromere autoantigen centromere protein C (CENP-C); heterogeneity of anti-CENP-C response in rheumatic diseases. Sugimoto, K., Kuriyama, K., Himeno, M., Muro, Y. J. Rheumatol. (1998) [Pubmed]
Essential Role for Nuclear PTEN in Maintaining Chromosomal Integrity. Shen, W.H., Balajee, A.S., Wang, J., Wu, H., Eng, C., Pandolfi, P.P., Yin, Y. Cell (2007) [Pubmed]
CENP-C, an autoantigen in scleroderma, is a component of the human inner kinetochore plate. Saitoh, H., Tomkiel, J., Cooke, C.A., Ratrie, H., Maurer, M., Rothfield, N.F., Earnshaw, W.C. Cell (1992) [Pubmed]
Mapping the assembly pathways that specify formation of the trilaminar kinetochore plates in human cells. Liu, S.T., Rattner, J.B., Jablonski, S.A., Yen, T.J. J. Cell Biol. (2006) [Pubmed]
In vitro modification of human centromere protein CENP-C fragments by small ubiquitin-like modifier (SUMO) protein: definitive identification of the modification sites by tandem mass spectrometry analysis of the isopeptides. Chung, T.L., Hsiao, H.H., Yeh, Y.Y., Shia, H.L., Chen, Y.L., Liang, P.H., Wang, A.H., Khoo, K.H., Shoei-Lung Li, S. J. Biol. Chem. (2004) [Pubmed]
Specific interaction between human kinetochore protein CENP-C and a nucleolar transcriptional regulator. Pluta, A.F., Earnshaw, W.C. J. Biol. Chem. (1996) [Pubmed]
FISH mapping of centromere protein C (CENPC) on human chromosome 4q31-->q21. Xie, Y., Heng, H.H. Cytogenet. Cell Genet. (1996) [Pubmed]
CENP-B interacts with CENP-C domains containing Mif2 regions responsible for centromere localization. Suzuki, N., Nakano, M., Nozaki, N., Egashira, S., Okazaki, T., Masumoto, H. J. Biol. Chem. (2004) [Pubmed]
Creation and characterization of temperature-sensitive CENP-C mutants in vertebrate cells. Fukagawa, T., Regnier, V., Ikemura, T. Nucleic Acids Res. (2001) [Pubmed]
CENP-C is required for maintaining proper kinetochore size and for a timely transition to anaphase. Tomkiel, J., Cooke, C.A., Saitoh, H., Bernat, R.L., Earnshaw, W.C. J. Cell Biol. (1994) [Pubmed]
Further evidence that CENP-C is a necessary component of active centromeres: studies of a dic(X; 15) with simultaneous immunofluorescence and FISH. Page, S.L., Earnshaw, W.C., Choo, K.H., Shaffer, L.G. Hum. Mol. Genet. (1995) [Pubmed]
Efficient conditional mutation of the vertebrate CENP-C gene. Fukagawa, T., Brown, W.R. Hum. Mol. Genet. (1997) [Pubmed]
RNAi knockdown of human kinetochore protein CENP-H. Orthaus, S., Ohndorf, S., Diekmann, S. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
Death Receptor-induced Apoptosis Reveals a Novel Interplay between the Chromosomal Passenger Complex and CENP-C during Interphase. Faragher, A.J., Sun, X.M., Butterworth, M., Harper, N., Mulheran, M., Ruchaud, S., Earnshaw, W.C., Cohen, G.M. Mol. Biol. Cell (2007) [Pubmed]
A dynamic connection between centromeres and ND10 proteins. Everett, R.D., Earnshaw, W.C., Pluta, A.F., Sternsdorf, T., Ainsztein, A.M., Carmena, M., Ruchaud, S., Hsu, W.L., Orr, A. J. Cell. Sci. (1999) [Pubmed]
Interphase-specific association of intrinsic centromere protein CENP-C with HDaxx, a death domain-binding protein implicated in Fas-mediated cell death. Pluta, A.F., Earnshaw, W.C., Goldberg, I.G. J. Cell. Sci. (1998) [Pubmed]
Mutational analysis of the central centromere targeting domain of human centromere protein C, (CENP-C). Song, K., Gronemeyer, B., Lu, W., Eugster, E., Tomkiel, J.E. Exp. Cell Res. (2002) [Pubmed]

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