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TRIM11 activates the proteasome and promotes overall protein degradation by regulating USP14

Author

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  • Liang Chen

    (University of Pennsylvania)

  • Guixin Zhu

    (University of Pennsylvania)

  • Eleanor M. Johns

    (University of Pennsylvania)

  • Xiaolu Yang

    (University of Pennsylvania)

Abstract

The proteasome is a complex protease critical for protein quality control and cell regulation, and its dysfunction is associated with cancer and other diseases. However, the mechanisms that control proteasome activity in normal and malignant cells remain unclear. Here we report that TRIM11 enhances degradation of aberrant and normal regulatory proteins, and augments overall rate of proteolysis. Mechanistically, TRIM11 binds to both the proteasome and USP14, a deubiquitinase that prematurely removes ubiquitins from proteasome-bound substrates and also noncatalytically inhibits the proteasome, and precludes their association, thereby increasing proteasome activity. TRIM11 promotes cell survival and is upregulated upon heat shock. Moreover, TRIM11 is required for tumor growth, and increased expression of TRIM11 correlates with poor clinical survival. These findings identify TRIM11 as an important activator of the proteasome, define a pathway that adjusts proteasome activity, and reveal a mechanism by which tumor cells acquire higher degradative power to support oncogenic growth.

Suggested Citation

  • Liang Chen & Guixin Zhu & Eleanor M. Johns & Xiaolu Yang, 2018. "TRIM11 activates the proteasome and promotes overall protein degradation by regulating USP14," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03499-z
    DOI: 10.1038/s41467-018-03499-z
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    Cited by:

    1. Ka Ying Sharon Hung & Sven Klumpe & Markus R. Eisele & Suzanne Elsasser & Geng Tian & Shuangwu Sun & Jamie A. Moroco & Tat Cheung Cheng & Tapan Joshi & Timo Seibel & Duco Dalen & Xin-Hua Feng & Ying L, 2022. "Allosteric control of Ubp6 and the proteasome via a bidirectional switch," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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