Journal
CELLULAR SIGNALLING
Volume 32, Issue -, Pages 24-35Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2017.01.015
Keywords
Mammalian target of rapamycin complex 1 (mTORC1); Rag GTPases; Nudix-type motif 2 (NUDT2); Lysosomal localization; Cancer cell proliferation
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Funding
- National Research Foundation of Korea (NRF) grant - Korea government (MEST) [NRF-2015R1A2A1A13001834, NRF-2016K1A1A2912722]
- National Research Foundation of Korea [2016K1A1A2912722] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Lysosomal localization of mammalian target of rapamycin complex 1 (mTORC1) is a critical step for activation of the molecule. Rag GTPases are essential for this translocation. Here, we demonstrate that Nudix-type motif 2 (NUDT2) is a novel positive regulator of mTORC1 activation. Activation of mTORC1 is impaired in NUDT2-silenced cells. Mechanistically, NUDT2 binds to Rag GTPase and controls mTORC1 translocation to the lysosomal membrane. Furthermore, NUDT2-dependent mTORC1 regulation is critical for proliferation of breast cancer cells, as NUDT2-silenced cells arrest in GO/G1 phases. Taken together, these results show that NUDT2 is a novel complex formation enhancing factor regulating mTORC1-Rag GTPase signaling that is crucial for cell growth control. (C) 2017 Elsevier Inc. All rights reserved.
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