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Phosphorylated MED1 links transcription recycling and cancer growth.

Publication ,  Journal Article
Chen, Z; Ye, Z; Soccio, RE; Nakadai, T; Hankey, W; Zhao, Y; Huang, F; Yuan, F; Wang, H; Cui, Z; Sunkel, B; Wu, D; Dzeng, RK; Huang, THM ...
Published in: Nucleic Acids Res
May 6, 2022

Mediator activates RNA polymerase II (Pol II) function during transcription, but it remains unclear whether Mediator is able to travel with Pol II and regulate Pol II transcription beyond the initiation and early elongation steps. By using in vitro and in vivo transcription recycling assays, we find that human Mediator 1 (MED1), when phosphorylated at the mammal-specific threonine 1032 by cyclin-dependent kinase 9 (CDK9), dynamically moves along with Pol II throughout the transcribed genes to drive Pol II recycling after the initial round of transcription. Mechanistically, MED31 mediates the recycling of phosphorylated MED1 and Pol II, enhancing mRNA output during the transcription recycling process. Importantly, MED1 phosphorylation increases during prostate cancer progression to the lethal phase, and pharmacological inhibition of CDK9 decreases prostate tumor growth by decreasing MED1 phosphorylation and Pol II recycling. Our results reveal a novel role of MED1 in Pol II transcription and identify phosphorylated MED1 as a targetable driver of dysregulated Pol II recycling in cancer.

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Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

May 6, 2022

Volume

50

Issue

8

Start / End Page

4450 / 4463

Location

England

Related Subject Headings

  • Transcription, Genetic
  • RNA Polymerase II
  • Phosphorylation
  • Neoplasms
  • Mediator Complex Subunit 1
  • Mediator Complex
  • Mammals
  • Male
  • Humans
  • Developmental Biology
 

Citation

APA
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ICMJE
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Chen, Z., Ye, Z., Soccio, R. E., Nakadai, T., Hankey, W., Zhao, Y., … Wang, Q. (2022). Phosphorylated MED1 links transcription recycling and cancer growth. Nucleic Acids Res, 50(8), 4450–4463. https://doi.org/10.1093/nar/gkac246
Chen, Zhong, Zhenqing Ye, Raymond E. Soccio, Tomoyoshi Nakadai, William Hankey, Yue Zhao, Furong Huang, et al. “Phosphorylated MED1 links transcription recycling and cancer growth.Nucleic Acids Res 50, no. 8 (May 6, 2022): 4450–63. https://doi.org/10.1093/nar/gkac246.
Chen Z, Ye Z, Soccio RE, Nakadai T, Hankey W, Zhao Y, et al. Phosphorylated MED1 links transcription recycling and cancer growth. Nucleic Acids Res. 2022 May 6;50(8):4450–63.
Chen, Zhong, et al. “Phosphorylated MED1 links transcription recycling and cancer growth.Nucleic Acids Res, vol. 50, no. 8, May 2022, pp. 4450–63. Pubmed, doi:10.1093/nar/gkac246.
Chen Z, Ye Z, Soccio RE, Nakadai T, Hankey W, Zhao Y, Huang F, Yuan F, Wang H, Cui Z, Sunkel B, Wu D, Dzeng RK, Thomas-Ahner JM, Huang THM, Clinton SK, Huang J, Lazar MA, Jin VX, Roeder RG, Wang Q. Phosphorylated MED1 links transcription recycling and cancer growth. Nucleic Acids Res. 2022 May 6;50(8):4450–4463.
Journal cover image

Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

May 6, 2022

Volume

50

Issue

8

Start / End Page

4450 / 4463

Location

England

Related Subject Headings

  • Transcription, Genetic
  • RNA Polymerase II
  • Phosphorylation
  • Neoplasms
  • Mediator Complex Subunit 1
  • Mediator Complex
  • Mammals
  • Male
  • Humans
  • Developmental Biology