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

Liang Chen, Guixin Zhu, Eleanor M. Johns and Xiaolu Yang ()
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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

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03499-z

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