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  • Brief Communications Arising
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Control of proteasomal proteolysis by mTOR

Nature volume 529, pages E1–E2 (2016)Cite this article

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ARISING FROM Y. Zhang et al. Nature 513, 440–443 (2014); doi:10.1038/nature13492

Among the best-studied anabolic actions of mTORC1 are enhancing protein synthesis and inhibiting protein degradation by autophagy1,2. When mTORC1 is inactivated during starvation, proteolysis and autophagy increase to provide amino acids for protein synthesis and energy production. However, Zhang et al. recently reported that inhibition of mTORC1 activity for 16 h or more causes a reduction in overall proteolysis by decreasing proteasome expression3. However, their methodology to measure the rates of protein degradation and the rates obtained appear questionable. There is a Reply to this Brief Communication Arising by Zhang, Y. et al. Nature 529, http://dx.doi.org/10.1038/nature16473 (2016).

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Figure 1: Pulse-chase methodology using 3H-Phe allows valid measurements of degradation rates and shows that mTOR inhibition causes rapid and sustained increases in protein degradation by both proteasomal and lysosomal pathways in Tsc2-null MEFs.

References

  1. Laplante, M. & Sabatini, D. M. mTOR signaling in growth control and disease. Cell 149, 274–293 (2012)

    Article  CAS  Google Scholar 

  2. He, C. & Klionsky, D. J. Regulation mechanisms and signaling pathways of autophagy. Annu. Rev. Genet. 43, 67–93 (2009)

    Article  CAS  Google Scholar 

  3. Zhang, Y. et al. Coordinated regulation of protein synthesis and degradation by mTORC1. Nature 513, 440–443 (2014)

    Article  CAS  ADS  Google Scholar 

  4. Zhao, J., Zhai, B., Gygi, S. P. & Goldberg, A. L. mTOR inhibition activates overall protein degradation by the ubiquitin proteasome system as well as by autophagy. Proc. Natl Acad. Sci. USA http://dx.doi.org/10.1073/pnas.1521919112 (2015)

  5. Goldberg, A. L. & St John, A. C. Intracellular protein degradation in mammalian and bacterial cells: part 2. Annu. Rev. Biochem. 45, 747–804 (1976)

    Article  CAS  Google Scholar 

  6. Rock, K. L., Farfan-Arribas, D. J., Colbert, J. D. & Goldberg, A. L. Re-examining class-I presentation and the DRiP hypothesis. Trends Immunol. 35, 144–152 (2014)

    Article  CAS  Google Scholar 

  7. Zhao, J. et al. FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab. 6, 472–483 (2007)

    Article  CAS  Google Scholar 

  8. Brault, J. J., Jespersen, J. G. & Goldberg, A. L. Peroxisome proliferator-activated receptor γ coactivator 1α or 1β overexpression inhibits muscle protein degradation, induction of ubiquitin ligases, and disuse atrophy. J. Biol. Chem. 285, 19460–19471 (2010)

    Article  CAS  Google Scholar 

  9. Piccirillo, R. & Goldberg, A. L. The p97/VCP ATPase is critical in muscle atrophy and the accelerated degradation of muscle proteins. EMBO J. 31, 3334–3350 (2012)

    Article  CAS  Google Scholar 

  10. Sha, Z. & Goldberg, A. L. Proteasome-mediated processing of Nrf1 is essential for coordinate induction of all proteasome subunits and p97. Curr. Biol. 24, 1573–1583 (2014)

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cell Biology, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Jinghui Zhao & Alfred L. Goldberg

  2. Department of Chemistry, Cambridge University, Cambridge CB2 1EW, UK,

    Gonzalo A. Garcia

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  1. Jinghui Zhao
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  2. Gonzalo A. Garcia
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  3. Alfred L. Goldberg
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Correspondence to Alfred L. Goldberg.

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Zhao, J., Garcia, G. & Goldberg, A. Control of proteasomal proteolysis by mTOR. Nature 529, E1–E2 (2016). https://doi.org/10.1038/nature16472

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