Rabin8 Protein Interacts with GTPase Rheb and Inhibits Phosphorylation of Ser235/Ser236 in Small Ribosomal Subunit Protein S6

Cover Page

Cite item

Full Text

Abstract

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that in association with Raptor, mLST8, PRAS40 and Deptor forms a complex (mTORCl) playing the key role in the regulation of protein biosynthesis, transcription, cellular metabolism, apoptosis and autophagy; mainly via direct phosphorylation of S6 kinases. mTORC1 is activated by growth factors and amino acids via the activation of Rheb GTPase. In the current study, we demonstrate for the first time that the over-expression of Rabin8, which functions as a guanine nucleotide exchange factor for Rab8 GTPase, suppresses phosphorylation of Ser235/Ser236 in ribosomal protein S6. Downregulation of Rabin8 using small interfering RNA (siRNA) increases the phosphorylation of Ser235/Ser236 in ribosomal protein S6. Furthermore, Rabin8 can be immunoprecipitated with Rheb GTPase. These results suggest the existence of a novel mechanism of mTORC1 regulation and its downstream processes. Since Rabin8 is a known regulator of ciliogenesis, a potential link can exist between regulation of Rheb/ mTORC1 and ciliogenesis.

Full Text

Rabin8 Protein Interacts with GTPase Rheb and Inhibits Phosphorylation of Ser235/Ser236 in Small Ribosomal Subunit Protein S6
×

About the authors

А А Parkhitko

Pirogov Russian National Research Medical University; Fox Chase Cancer Center; Brigham and Women's Hospital, Harvard Medical School

Email: parhitko@mail.ru
Philadelphia, USA; USA

О О Favorova

Pirogov Russian National Research Medical University

E P Henske

Fox Chase Cancer Center; Brigham and Women's Hospital, Harvard Medical School

Philadelphia, USA; USA

References

  1. Sengupta S., Peterson T.R., Sabatini D.M. // Mol. Сell. 2010. V. 40. P. 310-322.
  2. Zoncu R., Efeyan A., Sabatini D.M. // Nat. Rev. Mol. Cell. Biol. 2011. V. 12. P. 21-35.
  3. Chan E.Y. // Sci. Signaling. 2009. V. 2. P. pe51.
  4. Mizushima N. // Curr. Opin. Cell Biol. 2010. V. 22. P. 132-139.
  5. Wullschleger S., Loewith R., Hall M.N. // Cell. 2006. V. 124. P. 471-484.
  6. Ma X.M., Blenis J. // Nat. Rev. Mol. Cell. Biol. 2009. V. 10. P. 307-318.
  7. Astrinidis A., Henske E.P. // Oncogene. 2005. V. 24. P. 7475-7481.
  8. Hartman T.R., Liu D., Zilfou J.T., Robb V., Morrison T., Watnick T., Henske E.P. // Hum. Mol. Genet. 2009. V. 18. P. 151-163.
  9. Nachury M.V., Loktev A.V., Zhang Q., Westlake C.J., Peranen J., Merdes A., Slusarski D.C., Scheller R.H., Bazan J.F., Sheffield V.C., et al. // Cell. 2007. V. 129. P. 1201-1213.
  10. Hattula K., Furuhjelm J., Arffman A., Peranen J. // Mol. Biol. Cell. 2002. V. 13. P. 3268-3280.
  11. Sancak Y., Bar-Peled L., Zoncu R., Markhard A.L., Nada S., Sabatini D.M. // Cell. 2010. V. 141. P. 290-303.
  12. Ruvinsky I., Sharon N., Lerer T., Cohen H., Stolovich-Rain M., Nir T., Dor Y., Zisman P., Meyuhas O. // Genes Dev. 2005. V. 19. P. 2199-2211.
  13. Peterson T.R., Laplante M., Thoreen C.C., Sancak Y., Kang S.A., Kuehl W.M., Gray N.S., Sabatini D.M. // Cell. 2009. V. 137. P. 873-886.
  14. Smith E.M., Finn S.G., Tee A.R., Browne G.J., Proud C.G. // J. Biol. Chem. 2005. V. 280. P. 18717-18727.
  15. Ballif B.A., Roux P.P., Gerber S.A., MacKeigan J.P., Blenis J., Gygi S.P. // Proc. Natl. Acad. Sci. USA. 2005. V. 102. P. 667-672.
  16. Manning B.D., Tee A.R., Logsdon M.N., Blenis J., Cantley L.C. // Mol. Cell. 2002. V. 10. P. 151-162.
  17. Hildebrandt F., Benzing T., Katsanis N. // N. Engl. J. Med. 2011. V. 364. P. 1533-1543.
  18. Mok C.A., Heon E., Zhen M. // Clin. Genet. 2010. V. 77. P. 18-27.
  19. Duldulao N.A., Li J., Sun Z. // Protein Cell. 2010. V. 1. P. 726-736.
  20. Courtney K.D., Corcoran R.B., Engelman J.A. // J. Clin. Oncol. 2010. V. 28. P. 1075-1083.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2011 Parkhitko А.А., Favorova О.О., Henske E.P.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies