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Cell signalling

mTOR targets its own inhibitor

Nature Reviews Molecular Cell Biology volume 12, page 769 (2011)Cite this article

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The authors of these papers all sought to identify the E3 ligase that triggers DEPTOR degradation. Gao et al. overexpressed DEPTOR in cells and, using mass spectrometry, identified the F box protein β-transducin repeat-containing protein 2 (βTrCP2) as a DEPTOR-interacting protein. Zhao et al. examined DEPTOR for consensus binding motifs of F box proteins and identified βTrCP1 and βTrCP2 (which are thought to function redundantly) as DEPTOR-interacting proteins. Duan et al. screened a library of F box proteins, revealing that DEPTOR interacts with βTrCP1 and βTrCP2. Thus, SCFβTrCP is a candidate E3 ligase for DEPTOR. Indeed, further experiments by these groups confirmed that βTrCP induces DEPTOR degradation, and that DEPTOR must be phosphorylated within its degradation motif (known as a degron; 286-SSGYFS-291) to recruit βTrCP.

βTrCP induces DEPTOR degradation, and ... DEPTOR must be phosphorylated ... to recruit βTrCP.

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References

ORIGINAL RESEARCH PAPERS

  1. Gao, D. et al. mTOR drives its own activation via SCFβTrCP-dependent degradation of the mTOR inhibitor DEPTOR. Mol. Cell 44, 290–303 (2011) Article

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  2. Zhao, Y., Xiong, X. & Sun, Y. DEPTOR, an mTOR inhibitor, is a physiological substrate of SCFβTrCP E3 ubiquitin ligase and regulates survival and autophagy. Mol. Cell 44, 304–316 (2011) Article

    Article  CAS  Google Scholar 

  3. Duan, S. et al. mTOR generates an auto-amplification loop by triggering the βTrCP- and CK1α-dependent degradation of DEPTOR. Mol. Cell 44, 317–324 (2011) Article

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FURTHER READING

  1. Zoncu, R., Efeyan, A. & Sabatini, D. M. mTOR: from growth signal integration to cancer, diabetes and ageing. Nature Rev. Mol. Cell Biol. 12, 21–35 (2011)

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Authors
  1. Katharine H. Wrighton
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Wrighton, K. mTOR targets its own inhibitor. Nat Rev Mol Cell Biol 12, 769 (2011). https://doi.org/10.1038/nrm3229

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