title: Nudix-type motif 2 contributes to cancer proliferation through the regulation of Rag GTPase-mediated mammalian target of rapamycin complex 1 localization.
abstract: 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.
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea.
authors.forename: Ohman
authors.initials: O
authors.lastname: Kwon
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea.
authors.forename: Dongoh
authors.initials: D
authors.lastname: Kwak
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ha
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea.
authors.forename: Hyeona
authors.initials: H
authors.lastname: Jeon
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea.
authors.forename: Mangeun
authors.initials: M
authors.lastname: Park
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea.
authors.forename: Yeonho
authors.initials: Y
authors.lastname: Chang
authors.affiliation: School of Nano-Biotechnology and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Republic of Korea.
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea; Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea. Electronic address: sungho@postech.ac.kr.
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000378:metabolism*; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D000096964:Nudix Hydrolases
chemical_list: D000596:Amino Acids; D007328:Insulin; D000076222:Mechanistic Target of Rapamycin Complex 1; D020559:Monomeric GTP-Binding Proteins; D010744:Phosphoric Monoester Hydrolases; C484342:RRAGA protein, human; C557514:NUDT2 protein, human; D000096964:Nudix Hydrolases
keywords: Cancer cell proliferation; Lysosomal localization; Mammalian target of rapamycin complex 1 (mTORC1); Nudix-type motif 2 (NUDT2); Rag GTPases