MTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide

Won Jun Oh, Chang Chih Wu, Sung Jin Kim, Valeria Facchinetti, Louis André Julien, Monica Finlan, Philippe P. Roux, Bing Su, Estela Jacinto

Research output: Contribution to journalArticle

193 Citations (Scopus)

Abstract

The mechanisms that couple translation and protein processing are poorly understood in higher eukaryotes. Although mammalian target of rapamycin (mTOR) complex 1 (mTORC1) controls translation initiation, the function of mTORC2 in protein synthesis remains to be defined. In this study, we find that mTORC2 can colocalize with actively translating ribosomes and can stably interact with rpL23a, a large ribosomal subunit protein present at the tunnel exit. Exclusively during translation of Akt, mTORC2 mediates phosphorylation of the nascent polypeptide at the turn motif (TM) site, Thr450, to avoid cotranslational Akt ubiquitination. Constitutive TM phosphorylation occurs because the TM site is accessible, whereas the hydrophobic motif (Ser473) site is concealed in the ribosomal tunnel. Thus, mTORC2 can function cotranslationally by phosphorylating residues in nascent chains that are critical to attain proper conformation. Our findings reveal that mTOR links protein production with quality control.

Original languageEnglish (US)
Pages (from-to)3939-3951
Number of pages13
JournalEMBO Journal
Volume29
Issue number23
DOIs
StatePublished - Dec 1 2010

Fingerprint

Phosphorylation
Ribosomes
Peptides
Tunnels
TOR Serine-Threonine Kinases
Large Ribosome Subunits
Ribosomal Proteins
Ubiquitination
Protein Subunits
Protein Biosynthesis
Sirolimus
Eukaryota
Quality Control
Quality control
Conformations
Proteins
TOR complex 2
Processing

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Keywords

  • AGC kinases
  • mTOR signalling
  • protein maturation
  • ribosomes
  • translation

Cite this

Oh, Won Jun ; Wu, Chang Chih ; Kim, Sung Jin ; Facchinetti, Valeria ; Julien, Louis André ; Finlan, Monica ; Roux, Philippe P. ; Su, Bing ; Jacinto, Estela. / MTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide. In: EMBO Journal. 2010 ; Vol. 29, No. 23. pp. 3939-3951.
@article{6f276647c33b4b0a8fbbbdc47335ad3f,
title = "MTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide",
abstract = "The mechanisms that couple translation and protein processing are poorly understood in higher eukaryotes. Although mammalian target of rapamycin (mTOR) complex 1 (mTORC1) controls translation initiation, the function of mTORC2 in protein synthesis remains to be defined. In this study, we find that mTORC2 can colocalize with actively translating ribosomes and can stably interact with rpL23a, a large ribosomal subunit protein present at the tunnel exit. Exclusively during translation of Akt, mTORC2 mediates phosphorylation of the nascent polypeptide at the turn motif (TM) site, Thr450, to avoid cotranslational Akt ubiquitination. Constitutive TM phosphorylation occurs because the TM site is accessible, whereas the hydrophobic motif (Ser473) site is concealed in the ribosomal tunnel. Thus, mTORC2 can function cotranslationally by phosphorylating residues in nascent chains that are critical to attain proper conformation. Our findings reveal that mTOR links protein production with quality control.",
keywords = "AGC kinases, mTOR signalling, protein maturation, ribosomes, translation",
author = "Oh, {Won Jun} and Wu, {Chang Chih} and Kim, {Sung Jin} and Valeria Facchinetti and Julien, {Louis Andr{\'e}} and Monica Finlan and Roux, {Philippe P.} and Bing Su and Estela Jacinto",
year = "2010",
month = "12",
day = "1",
doi = "10.1038/emboj.2010.271",
language = "English (US)",
volume = "29",
pages = "3939--3951",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "23",

}

Oh, WJ, Wu, CC, Kim, SJ, Facchinetti, V, Julien, LA, Finlan, M, Roux, PP, Su, B & Jacinto, E 2010, 'MTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide', EMBO Journal, vol. 29, no. 23, pp. 3939-3951. https://doi.org/10.1038/emboj.2010.271

MTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide. / Oh, Won Jun; Wu, Chang Chih; Kim, Sung Jin; Facchinetti, Valeria; Julien, Louis André; Finlan, Monica; Roux, Philippe P.; Su, Bing; Jacinto, Estela.

In: EMBO Journal, Vol. 29, No. 23, 01.12.2010, p. 3939-3951.

Research output: Contribution to journalArticle

TY - JOUR

T1 - MTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide

AU - Oh, Won Jun

AU - Wu, Chang Chih

AU - Kim, Sung Jin

AU - Facchinetti, Valeria

AU - Julien, Louis André

AU - Finlan, Monica

AU - Roux, Philippe P.

AU - Su, Bing

AU - Jacinto, Estela

PY - 2010/12/1

Y1 - 2010/12/1

N2 - The mechanisms that couple translation and protein processing are poorly understood in higher eukaryotes. Although mammalian target of rapamycin (mTOR) complex 1 (mTORC1) controls translation initiation, the function of mTORC2 in protein synthesis remains to be defined. In this study, we find that mTORC2 can colocalize with actively translating ribosomes and can stably interact with rpL23a, a large ribosomal subunit protein present at the tunnel exit. Exclusively during translation of Akt, mTORC2 mediates phosphorylation of the nascent polypeptide at the turn motif (TM) site, Thr450, to avoid cotranslational Akt ubiquitination. Constitutive TM phosphorylation occurs because the TM site is accessible, whereas the hydrophobic motif (Ser473) site is concealed in the ribosomal tunnel. Thus, mTORC2 can function cotranslationally by phosphorylating residues in nascent chains that are critical to attain proper conformation. Our findings reveal that mTOR links protein production with quality control.

AB - The mechanisms that couple translation and protein processing are poorly understood in higher eukaryotes. Although mammalian target of rapamycin (mTOR) complex 1 (mTORC1) controls translation initiation, the function of mTORC2 in protein synthesis remains to be defined. In this study, we find that mTORC2 can colocalize with actively translating ribosomes and can stably interact with rpL23a, a large ribosomal subunit protein present at the tunnel exit. Exclusively during translation of Akt, mTORC2 mediates phosphorylation of the nascent polypeptide at the turn motif (TM) site, Thr450, to avoid cotranslational Akt ubiquitination. Constitutive TM phosphorylation occurs because the TM site is accessible, whereas the hydrophobic motif (Ser473) site is concealed in the ribosomal tunnel. Thus, mTORC2 can function cotranslationally by phosphorylating residues in nascent chains that are critical to attain proper conformation. Our findings reveal that mTOR links protein production with quality control.

KW - AGC kinases

KW - mTOR signalling

KW - protein maturation

KW - ribosomes

KW - translation

UR - http://www.scopus.com/inward/record.url?scp=78649712949&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649712949&partnerID=8YFLogxK

U2 - 10.1038/emboj.2010.271

DO - 10.1038/emboj.2010.271

M3 - Article

C2 - 21045808

AN - SCOPUS:78649712949

VL - 29

SP - 3939

EP - 3951

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 23

ER -