Disease relevance of CENPH

• Centromere protein H is up-regulated in primary human colorectal cancer and its overexpression induces aneuploidy [1].
• Increased expression of CENP-H gene in human oral squamous cell carcinomas harboring high-proliferative activity [2].

High impact information on CENPH

• We have analyzed a functional human centromere and defined a region of increased chromosome scaffold/matrix attachment that overlaps three other distinct and nonoverlapping domains for constitutive centromere proteins CENP-A and CENP-H, and heterochromatin protein HP1 [3].
• Here, we isolated a multi-subunit complex, which includes the established inner kinetochore components CENP-H and CENP-I, and nine other proteins, from both human and chicken cells [4].
• The checkpoint protein BubR1, the fibrous corona component centromere protein (CENP) E, and the inner kinetochore proteins CENP-A and CENP-H also failed to accumulate to wild-type levels in depleted cells [5].
• Coimmunoprecipitation experiments revealed that CENP-50 interacted with the CENP-H/CENP-I complex in chicken DT40 cells [6].
• Moreover, CENP-H stable transfectant of mouse embryonic fibroblast/3T3 cell lines showed aberrant interphase micronuclei, characteristic of chromosome missegregation [1].

Biological context of CENPH

• Several centromere proteins such as CENP-A and CENP-H are the fundamental components of the human active kinetochore, and inappropriate expression of the centromere proteins could be a major cause of CIN [1].
• In these CENP-H overexpressed cells, CENP-H completely disappeared from the centromere of mitotic chromosomes, which might be the cause of the chromosome segregation defect [1].
• These results suggest that the aberrant expression and localization of a kinetochore protein CENP-H plays an important role in the aneuploidy frequently observed in colorectal cancers [1].
• Surprisingly, transient transfection of CENP-H expression plasmid into the diploid cell line HCT116 remarkably induced aneupoidy [1].
• Furthermore, time-course experiments revealed that transient treatment with 17-AAG between late S and G2/M phases causes substantial delocalization of CENP-H and CENP-I, a finding that strongly suggests that HSP90 participates in kinetochore assembly in a cell cycle-dependent manner [7].

Anatomical context of CENPH

• In this study, we show that CENP-H was also up-regulated in all of 15 primary human colorectal cancer tissues as well as in CIN tumor cell lines [1].
• RESULTS: Reverse transcription-PCR and Western blot showed that the expression level of CENP-H was higher in NPC cell lines and in immortalized nasopharyngeal epithelial cells than in the normal nasopharyngeal epithelial cell line at both transcriptional and translational levels [8].

Other interactions of CENPH

• 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 [9].
• In CENP-H knocked-down human cells, the misaligned chromosomes contained only reduced levels of CENP-E [9].
• Centromeric localization of CENP-50 was abolished in both CENP-H- and CENP-I-deficient cells [6].
• A significant correlation between the expression levels of CENP-H protein and the Ki-67 labeling index was found (Mann-Whitney U test, P=0.005) [2].

Analytical, diagnostic and therapeutic context of CENPH

• Using immunohistochemistry, we analyzed CENP-H protein expression in 160 clinicopathologically characterized NPC cases [8].
• We examined the expression of Centromere protein H (CENP-H) mRNA in 38 oral squamous cell carcinomas (SCCs), 2 epithelial dysplasias and 5 normal gingivae using the real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) [2].

References