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The transrepression and transactivation roles of CtBPs in the pathogenesis of different diseases

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Abstract

Gene transcription is strictly controlled by transcriptional complexes, which are assemblies of transcription factors, transcriptional regulators, and co-regulators. Mammalian genomes encode two C-terminal-binding proteins (CtBPs), CtBP1 and CtBP2, which are both well-known transcriptional corepressors of oncogenic processes. Their overexpression in tumors is associated with malignant behavior, such as uncontrolled cell proliferation, migration, and invasion, as well as with an increase in the epithelial-mesenchymal transition. CtBPs coordinate with other transcriptional regulators, such as histone deacetylases (HDACs) and histone acetyltransferases (p300 and CBP [CREBP-binding protein]) that contain the PXDLS motif, and with transcription factors to assemble transcriptional complexes that dock onto the promoters of genes to initiate gene transcription. Emerging evidence suggests that CtBPs function as both corepressors and coactivators in different biological processes ranging from apoptosis to inflammation and osteogenesis. Therapeutic targeting of CtBPs or the interactions required to form transcriptional complexes has also shown promising effects in preventing disease progression. This review summarizes the most recent progress in the study of CtBP functions and therapeutic inhibitors in different biological processes. This knowledge may enable a better understanding of the complexity of the roles of CtBPs, while providing new insights into therapeutic strategies that target CtBPs.

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Funding

This study was supported by the Key Research and Development Project of Jiangxi Province (Social Development Field, No. 20202BBGL73059).

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  1. Department of Emergency, Jiangxi Provincial People’s Hospital Affiliated To Nanchang University, Nanchang, 330006, Jiangxi, China

    Zhi Chen

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Chen, Z. The transrepression and transactivation roles of CtBPs in the pathogenesis of different diseases. J Mol Med 99, 1335–1347 (2021). https://doi.org/10.1007/s00109-021-02107-w

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  • DOI: https://doi.org/10.1007/s00109-021-02107-w

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