NDLI: The small GTPase RALA controls c-Jun N-terminal kinase-mediated FOXO activation by regulation of a JIP1 scaffold complex.

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The small GTPase RALA controls c-Jun N-terminal kinase-mediated FOXO activation by regulation of a JIP1 scaffold complex.

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The small GTPase RALA controls c-Jun N-terminal kinase-mediated FOXO activation by regulation of a JIP1 scaffold complex.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Van Den Berg, Maaike C. W. Smits, Alida M. M. Polderman, Paulien E. Van Gogh, Inkie J. A. Van Triest, Miranda Vliem, Marjolein J. Burgering, Boudewijn M. T. Rehmann, Holger Visscher, Marieke Dansen, Tobias B.
Description	Author Affiliation: van den Berg MC ( Molecular Cancer Research, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands.)
Abstract	FOXO (forkhead box O) transcription factors are tumor suppressors and increase the life spans of model organisms. Cellular stress, in particular oxidative stress caused by an increase in levels of reactive oxygen species (ROS), activates FOXOs through JNK-mediated phosphorylation. Importantly, JNK regulation of FOXO is evolutionarily conserved. Here we identified the pathway that mediates ROS-induced JNK-dependent FOXO regulation. Following increased ROS, RALA is activated by the exchange factor RLF (RalGDS-like factor), which is in complex with JIP1 (C-Jun-amino-terminal-interacting protein 1) and JNK. Active RALA consequently regulates assembly and activation of MLK3, MKK4, and JNK onto the JIP1 scaffold. Furthermore, regulation of FOXO by RALA and JIP1 is conserved in C. elegans, where both ral-1 and jip-1 depletion impairs heat shock-induced nuclear translocation of the FOXO orthologue DAF16.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	30
Volume Number	288
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2013-07-26
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adaptor Proteins, Signal Transducing Metabolism Mitogen-Activated Protein Kinase 8 Transcription Factors Ral GTP-Binding Proteins Active Transport, Cell Nucleus Genetics Animals Blotting, Western Caenorhabditis Elegans Caenorhabditis Elegans Proteins Cell Nucleus Enzyme Activation HEK293 Cells MAP Kinase Kinase Kinases Mice Mutation NIH 3T3 Cells RNA Interference Reactive Oxygen Species Reverse Transcriptase Polymerase Chain Reaction Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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