Nudix-type motif 2 contributes to cancer proliferation through the regulation of Rag GTPase-mediated mammalian target of rapamycin complex 1 localization
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- Nudix-type motif 2 contributes to cancer proliferation through the regulation of Rag GTPase-mediated mammalian target of rapamycin complex 1 localization
- Kwon, Ohman; Kwak, Dongoh; Ha, Sang Hoon; Jeon, Hyeona; Park, Mangeun; Chang, Yeonho; Suh, Pann-Ghill; Ryu S.H.
- Mammalian target of rapamycin complex 1 (mTORC1); Rag GTPases; Nudix-type motif 2 (NUDT2); Lysosomal localization; Cancer cell proliferation
- Issue Date
- ELSEVIER SCIENCE INC
- CELLULAR SIGNALLING, v.32, no., pp.24 - 35
- 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 G0/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.
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