Role of the chromobox protein CBX7 in carcinogenesis
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Date
2015
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Faculty of Medicine, University of Kelaniya
Abstract
Introduction: Chromobox Protein Homolog 7 (CBX7) is a 251 amino acid
nuclear protein that contains one N-terminal chromo domain and one C-terminal
Pc box. Highly expressed in kidney, brain, heart and skeletal muscle, with weaker
expression in peripheral blood leukocytes. The CBX7 functions as a component
of the chromatin-associated Polycomb complex (PcG) and is involved in
maintaining the transcriptionally repressed state of target genes. Additionally,
CBX7 modifies chromatin and is thought to extend the cellular life span of
epithelial cells by repressing p14 ARF expression, while simultaneously
repressing telomerase activity. Due to its ability to repress the transcription of cellcycle
related proteins, CBX7 is thought to play a role in tumorigenesis, specifically
in the development of follicular lymphoma and thyroid cancer.
Objective: To study on oncogenic activity of CBX7 in humans.
Methodology: Expression pattern of CBX7 in a range of normal human tissues
and tumor samples was tested to determine oncogenic activity of CBX7.
Results: We found in different studies that CBX7 negatively or positively
regulates the expression of several genes (SPP1, SPINK1, STEAP1, and FOS,
FOSB, EGR1) associated to cancer progression, by interacting with their promoter
regions and modulating their transcriptional activity. Furthermore, Cbx7 repressed
transcription from the Ink4a/Arf locus and acted epistatically to the Arf-p53
pathway during tumorigenesis. Data identify CBX7 as a chromobox protein
causally linked to cancer development and may help to explain the low frequency
of INK4a/ARF mutations observed in human follicular lymphoma.
Discussion: Mechanism by which the loss of CBX7 expression may contribute to
the emergence of a more malignant phenotype and the loss of CBX7 expression
might play a critical role in advanced stages of carcinogenesis by deregulating the
expression of specific effector genes.
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Simair, Altaf Ahmed and Lu, Changrui, 2015. Role of the chromobox protein CBX7 in carcinogenesis. Proceedings of the International Workshop on Molecular Biology Techniques Related to Infectious/Genetic Diseases & Human Identification, Molecular Medicine Unit, Faculty of Medicine, University of Kelaniya.