The TRE17 oncogene encodes a component of a novel effector pathway for Rho GTPases Cdc42 and Rac1 and stimulates actin remodeling.
The Rho family GTPases Cdc42 and Rac1 play fundamental roles in transformation and actin remodeling. Here, we demonstrate that the TRE17 oncogene encodes a component of a novel effector pathway for these GTPases. TRE17 coprecipitated specifically with the active forms of Cdc42 and Rac1 in vivo. Furthermore, the subcellular localization of TRE17 was dramatically regulated by these GTPases and mitogens. Under serum-starved conditions, TRE17 localized predominantly to filamentous structures within the cell. Epidermal growth factor (EGF) induced relocalization of TRE17 to the plasma membrane in a Cdc42-/Rac1-dependent manner. Coexpression of activated alleles of Cdc42 or Rac1 also caused complete redistribution of TRE17 to the plasma membrane, where it partially colocalized with the GTPases in filopodia and ruffles, respectively. Membrane recruitment of TRE17 by EGF or the GTPases was dependent on actin polymerization. Finally, we found that a C-terminal truncation mutant of TRE17 induced the accumulation of cortical actin, mimicking the effects of activated Cdc42. Together, these results identify TRE17 as part of a novel effector complex for Cdc42 and Rac1, potentially contributing to their effects on actin remodeling. The present study provides insights into the regulation and cellular function of this previously uncharacterized oncogene.
Masuda-Robens
Jeffrey M
JM
Department of Pharmacology, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USA.
Kutney
Sara N
SN
Qi
Hongwei
H
Chou
Margaret M
MM
D008841:Actin Cytoskeleton / Q000502:physiology / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism*; D019943:Amino Acid Substitution; D000818:Animals; D001704:Biopolymers; D019556:COS Cells; D002522:Chlorocebus aethiops; D016895:Culture Media, Serum-Free; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D010450:Endopeptidases; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000502:physiology; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008954:Models, Biological; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D009857:Oncogenes; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D011518:Proto-Oncogene Proteins; D011554:Pseudopodia / Q000737:chemistry / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013329:Structure-Activity Relationship; D014162:Transfection; D020798:Two-Hybrid System Techniques; D043222:Ubiquitin Thiolesterase; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*
D000199:Actins; D001704:Biopolymers; D016895:Culture Media, Serum-Free; D046911:Macromolecular Substances; D008565:Membrane Proteins; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor; D006160:Guanosine Triphosphate; D010450:Endopeptidases; C473330:USP6 protein, human; D043222:Ubiquitin Thiolesterase; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein