Open Access

The role of mediator subunit 12 in tumorigenesis and cancer therapeutics (Review)

  • Authors:
    • Cristian G. Gonzalez
    • Shivani Akula
    • Marieke Burleson
  • View Affiliations

  • Published online on: January 10, 2022     https://doi.org/10.3892/ol.2022.13194
  • Article Number: 74
  • Copyright: © Gonzalez et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mediator complex subunit 12 (MED12) is a subunit of Mediator, a large multi‑subunit protein complex that acts an important regulator of transcription. Specifically, MED12 is an integral part of the kinase module of Mediator along with MED13, CyclinC (CycC) and CDK8. Structural studies have indicated that MED12 makes a direct connection to CycC through a specific interface and thereby functions to create a link between MED13 and CycC‑CDK8. Disruption of the MED12‑CycC interface often leads to dysregulated CDK8 kinase activity, which has important physiological implications. For example, a number of studies have indicated that mutations within MED12 can lead to the formation of benign or malignant tumors, either as a result of MED12‑CycC disruption or through distinct independent mechanisms. Furthermore, recent studies have indicated that the N‑terminal portion of MED12 forms a direct connection to CDK8. Mutations within MED12 do not appear to disrupt the physical connection to CDK8, but rather abrogate CDK8 kinase activity. Thus, mutations in MED12 can cause disruption of CDK8 kinase activity through two separate mechanisms. The aim of the present review article was to discuss the MED12 mutational landscape in a variety of benign and malignant tumors, as well as the mechanistic basis behind tumorigenesis. Furthermore, the link between MED12 and drug resistance has also been discussed, as well as potential cancer therapeutics related to MED12‑altered tumors.
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March-2022
Volume 23 Issue 3

Print ISSN: 1792-1074
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Spandidos Publications style
Gonzalez CG, Akula S and Burleson M: The role of mediator subunit 12 in tumorigenesis and cancer therapeutics (Review). Oncol Lett 23: 74, 2022
APA
Gonzalez, C.G., Akula, S., & Burleson, M. (2022). The role of mediator subunit 12 in tumorigenesis and cancer therapeutics (Review). Oncology Letters, 23, 74. https://doi.org/10.3892/ol.2022.13194
MLA
Gonzalez, C. G., Akula, S., Burleson, M."The role of mediator subunit 12 in tumorigenesis and cancer therapeutics (Review)". Oncology Letters 23.3 (2022): 74.
Chicago
Gonzalez, C. G., Akula, S., Burleson, M."The role of mediator subunit 12 in tumorigenesis and cancer therapeutics (Review)". Oncology Letters 23, no. 3 (2022): 74. https://doi.org/10.3892/ol.2022.13194