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: Ohman Kwon, Dongoh Kwak, Sang Hoon Ha, Hyeona Jeon, Mangeun Park, Yeonho Chang, Pann-Ghill Suh, Sung Ho Ryu
• Journal: Cellular signalling (Cell Signal) Vol. 32 Pg. 24-35 (04 2017) ISSN: 1873-3913 [Electronic] England
• PMID: 28089905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Amino Acids
• Insulin
• Mechanistic Target of Rapamycin Complex 1
• Phosphoric Monoester Hydrolases
• RRAGA protein, human
• NUDT2 protein, human
• Monomeric GTP-Binding Proteins

Topics

• Amino Acids (pharmacology)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• G1 Phase (drug effects)
• Gene Knockdown Techniques
• Humans
• Insulin (pharmacology)
• Lysosomes (drug effects, metabolism)
• Mechanistic Target of Rapamycin Complex 1 (metabolism)
• Monomeric GTP-Binding Proteins (metabolism)
• Neoplasms (metabolism, pathology)
• Phosphoric Monoester Hydrolases (metabolism)
• Protein Binding (drug effects)
• Protein Multimerization (drug effects)
• Resting Phase, Cell Cycle (drug effects)
• Signal Transduction (drug effects)
• Tumor Stem Cell Assay