Topic
CENPH
About: CENPH is a research topic. Over the lifetime, 4 publications have been published within this topic receiving 33 citations. The topic is also known as: centromere protein H.
Papers
TL;DR: Results indicate that Sp1 and Sp3 bind to the CenPH minimal promoter and function as a regulator of the transcription of CENPH in human nasopharyngeal carcinomas.
Abstract: The overexpression of centromere protein H (CENPH), one of the fundamental components of the human active kinetochore, has been shown to be closely associated with human cancers. However, the mechanism of its transcriptional regulation has not been reported. The aim of the present study was to investigate the regulatory elements for the transcriptional regulation of CENPH in nasopharyngeal carcinoma cells. To characterize the CENPH promoter and identify regulatory elements, we cloned 1015 bp (−975/+40 bp) of the 5′-flanking region of the CENPH gene from immortalized normal nasopharyngeal epithelial cells (Bmi-1/NPEC). Functional analysis established a minimal region (−140/−87 bp) involved in the regulation of human CENPH promoter activity. Through site-directed mutagenesis, a transactivation assay, chromatin immunoprecipitation, and electrophoretic mobility shift assay, we found that the Sp1/Sp3 transcription factors could bind to the CENPH promoter in vitro and in vivo, and that they regulated CENPH promoter activation in human nasopharyngeal carcinoma cells. Furthermore, Sp1 and Sp3 were highly expressed in nasopharyngeal carcinoma cells. Knockdown of Sp1 and Sp3 by small interfering RNA or inhibition of Sp1 and Sp3 activity by mithramycin A decreased CENPH mRNA expression, whereas the exogenous expression of Sp1 and Sp3 upregulated CENPH mRNA expression. Taken together, our results indicate that Sp1 and Sp3 bind to the CENPH minimal promoter and function as a regulator of the transcription of CENPH in human nasopharyngeal carcinomas.
14 citations
TL;DR: It is suggested that genetic variation may partly explain interindividual variation in the formation of CAs in the presence and absence of environmental genotoxic exposure.
Abstract: Genomic instability is a characteristic of a majority of human malignancies. Chromosomal instability is a common form of genomic instability that can be caused by defects in mitotic checkpoint genes. Chromosomal aberrations in peripheral blood are also indicative of genotoxic exposure and potential cancer risk. We evaluated associations between inherited genetic variants in 33 mitotic checkpoint genes and the frequency of chromosomal aberrations (CAs) in the presence and absence of environmental genotoxic exposure. Associations with both chromosome and chromatid type of aberrations were evaluated in two cohorts of healthy individuals, namely an exposed and a reference group consisting of 607 and 866 individuals, respectively. Binary logistic and linear regression analyses were performed for the association studies. Bonferroni-corrected significant p-value was 5 × 10-4 for 99 tests based on the number of analyzed genes and phenotypes. In the reference group the most prominent associations were found with variants in CCNB1, a master regulator of mitosis, and in genes involved in kinetochore function, including CENPH and TEX14, whereas in the exposed group the main association was found with variants in TTK, also an important gene in kinetochore function. How the identified variants may affect the fidelity of mitotic checkpoint remains to be investigated, however, the present study suggests that genetic variation may partly explain interindividual variation in the formation of CAs.
4 citations
TL;DR: Two opposing proteins involved in the SUMO pathway control assembly of the structures, [Mukhopadhyay et al.], reveal.
Abstract: Kinetochore formation involves some SUMO wrestling. Two opposing proteins involved in the SUMO pathway control assembly of the structures, [Mukhopadhyay et al.][1] reveal.
![Figure][2]
The kinetochore protein CenpH (green in left panel) vanishes when SENP6 is absent (right).
Addition of a
1 citations
TL;DR: This study demonstrates that CENPI, a centromere protein that localizes to the inner kinetochore structure, is a human autoantigen.
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2020 | 1 |
| 2012 | 1 |
| 2011 | 1 |
| 2010 | 1 |