Disease relevance of CENPB

• The DNA binding domain has been delimited within the NH2-terminal 125-amino acid region containing four potential alpha-helices using truncated CENP-B made in Escherichia coli cells [1].
• The cDNA was inserted into a modified baculovirus transfer vector which mediated high-level expression of recombinant human CENP-B with a histidine-hexapeptide as affinity ligand at its N-terminus in infected Spodoptera frugiperda (Sf9) insect cells [2].
• An ELISA established with the eukaryotically expressed and purified recombinant human full-length CENP-B demonstrated its excellent specificity, sensitivity and reproducibility for the measurement of autoantibodies directed to the human CENP-B (ACA-B) representing a diagnostic marker for CREST syndrome, an autoimmune rheumatic disease [2].
• Development of a CENP-A/CENP-B-specific immune response in a patient with systemic sclerosis [3].
• The immediate-early (IE) protein of HSV-1, which activates HIV-1 regulatory functions, contains three homologies to the 70-kDa antigen (two hexamers and a pentamer) and two to CENP-B (a hexamer and pentamer) [4].

Psychiatry related information on CENPB

• The idiotypes (Ids) of anticentromere antibodies (ACA) have been studied using a fusion protein obtained from cloned cDNA of the major centromere antigen, CENP-B, for isolation of the autoantibodies [5].

High impact information on CENPB

• We show that the CENP-B homologs are functionally redundant at centromeres, and that Abp1 binds specifically to centromeric heterochromatin [6].
• Using the chromatin immunoprecipitation assay, we found that direct assembly of CENP-A and CENP-B in cells with synthetic alphoid DNA required functional CENP-B boxes [7].
• CENP-B box is required for de novo centromere chromatin assembly on human alphoid DNA [7].
• A centromere DNA-binding protein from fission yeast affects chromosome segregation and has homology to human CENP-B [8].
• Comparison of the amino acid sequence of CENP-B with related proteins raises the possibility that CENP-B might share the ability to cause single-stranded DNA breaks [9].

Biological context of CENPB

• The family of three structurally related autoantigens CENP-A (17 kD), CENP-B (80 kD), and CENP-C (140 kD) are the best characterized components of the human centromere, and they have been widely assumed to be components of the kinetochore [10].
• In the present study we have mapped the distribution of CENP-B in mitotic chromosomes by immunoelectron microscopy using two monospecific polyclonal antibodies together with a newly developed series of ultra-small 1-nm colloidal gold probes [10].
• Although in certain instances CENP-B can be seen to be concentrated immediately adjacent to the lower surface of the kinetochore, the outer plate remains virtually unlabeled [10].
• These results suggest that the primary mechanism for localization of CENP-B to centromeres involves the recognition of a DNA sequence found at centromeres [11].
• The alphoid DNA-CENP-B (centromere protein B) complex is the first sequence-specific DNA/protein complex detected in the centromeric region of human chromosomes [1].

Anatomical context of CENPB

• Expression of epitope-tagged deletion derivatives of CENP-B in HeLa cells revealed that a single domain less than 158 residues from the amino terminus of the protein is sufficient to localize CENP-B to centromeres [11].
• Domains in the CENP-B polypeptide involved in the formation of complex A were determined in the present study with truncated derivatives expressed in Escherichia coli and in rabbit reticulocyte lysates [12].
• CENP-B mRNA was detected in mouse cells and tissues and an immunoreactive nuclear protein identical in size to human CENP-B was detected in mouse 3T3 cells using human ACA [13].
• Like CENP-B and C, but unlike CENP-A, this protein remained with the nuclear matrix after intensive extraction [14].
• We have studied the ability of the two main human centromere proteins CENP-A (18 kD) and CENP-B (80 kD) to bind tubulin, in order to correlate with one of the putative functional roles in spindle microtubule attachment [15].

Associations of CENPB with chemical compounds

• A human centromere protein, CENP-B, has a DNA binding domain containing four potential alpha helices at the NH2 terminus, which is separable from dimerizing activity [1].
• The carboxy terminus of CENP-B contains two long domains comprised almost entirely of glutamic and aspartic acid residues [16].
• The chromosome is negative for CBG banding and is devoid of detectable centromeric alpha satellite and its associated centromere protein CENP-B, suggesting activation of a neocentromere within the 1p32-36.1 region [17].
• Sera were analyzed by immunoprecipitation of [35S] methionine-labeled Ro 52, La, and CENP B and C generated by coupled in vitro transcription/translation [18].

Physical interactions of CENPB

• This result suggests that CENP-A nucleosomes form a complex with CENP-B and CENP-C through interaction with DNA [19].
• Hamster CENP-B protein analysis revealed at the N-terminal region a 133 amino acid fragment of 100% homology to the DNA binding motif identified previously for the human autoantigen [20].

Regulatory relationships of CENPB

• Several lines of evidence indicated that CENP-B binding subsequently stimulated the cross-talk between CCR3 and epidermal growth factor receptor (EGFR) via a matrix metalloprotease-dependent mechanism that involved the processing of heparin-binding EGF-like growth factor [21].

Other interactions of CENPB

• Despite this failure in HAC formation, centromere components (CENP-A, CENP-B and CENP-C) assembled at the integration sites correlating with a transcriptionally active state of both marker genes on the vector arms [22].
• Molecular cloning of cDNA for CENP-B, the major human centromere autoantigen [16].
• The results thus proved that CENP-B polypeptides form a homodimer at the COOH-terminal hydrophobic domain, each binding a DNA strand at their NH2-terminal domains [12].
• All of the low-alphoid centromeres are fully functional as indicated by their mitotic stability and binding to centromere proteins CENP-B, CENP-C, and CENP-E [23].
• 17-AAG caused delocalization of several kinetochore proteins including CENP-I and CENP-H but excluding CENP-B and CENP-C [24].

Analytical, diagnostic and therapeutic context of CENPB

• Quite unexpectedly, immunofluorescence analysis using antibodies specific for CENP-B reveals that the levels of antigen vary widely between chromosomes [16].
• Mapping of the human centromere protein B gene (CENPB) to chromosome 20p13 by fluorescence in situ hybridization [25].
• Based on the histidine-hexapeptide moiety, the recombinant CENP-B was purified to homogeneity by single-step affinity chromatography using metal chelating matrix [2].
• Antibody to CENP-B shows a 100% correlation with anti-centromere staining by indirect immunofluorescence [26].
• Anticentromere antibodies (ACAs) were assayed by immunofluorescence and immunoprecipitation of in vitro-translated centromere proteins (CENP-B and CENP-C) [27].

References