ABSTRACT The small GTPase RhoB suppresses cancer in part by limiting cell proliferation. However, the mechanisms it uses to achieve this are poorly understood. Recent studies link RhoB to

trafficking of Akt, which through its regulation of glycogen synthase kinase-3 (GSK-3) has an important role in controlling the stability of the c-Myc oncoprotein. c-Myc stabilization may be

a root feature of human tumorigenesis as it phenocopies an essential contribution of SV40 small T antigen in human cell transformation. In this study we show that RhoB directs efficient

turnover of c-Myc in established or transformed mouse fibroblasts and that the attenuation of RhoB which occurs commonly in human cancer is a sufficient cause to elevate c-Myc levels.

and degradation of c-Myc. RhoB deletion restricted nuclear localization of GSK-3, reduced T58 phosphorylation, and stabilized c-Myc. These effects were not associated with changes in

phosphorylation or localization of Akt, however, differences were observed in phosphorylation and localization of the GSK-3 regulatory Akt-related kinase, serum- and glucocorticoid-inducible

protein kinase (SGK). The ability of RhoB to support GSK-3-dependent turnover of c-Myc offers a mechanism by which RhoB acts to limit the proliferation of neoplastically transformed cells.

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support SIMILAR CONTENT BEING VIEWED BY OTHERS CRL2KLHDC3 AND CRL1FBXW7 COOPERATIVELY MEDIATE C-MYC DEGRADATION Article 02 May 2024 GFI1 UPREGULATES C-MYC EXPRESSION AND PROMOTES

C-MYC-DRIVEN CELL PROLIFERATION Article Open access 13 October 2020 RUNX3 INACTIVATES ONCOGENIC MYC THROUGH DISRUPTION OF MYC/MAX COMPLEX AND SUBSEQUENT RECRUITMENT OF GSK3Β-FBXW7 CASCADE

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ACKNOWLEDGEMENTS We thank J DuHadaway and PS Donover for providing expert technical assistance. This work was supported by NIH Grants CA82222 and CA100123 to GP and by the Lankenau Hospital

Foundation. MH is the recipient of an EB Churchman Research Fellowship. UK is supported by a DoD Breast Cancer Research Postdoctoral Fellowship. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *

Lankenau Institute for Medical Research, Wynnewood, PA, USA M Huang, U Kamasani & G C Prendergast * Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical School, Thomas

Jefferson University, Philadelphia, PA, USA G C Prendergast Authors * M Huang View author publications You can also search for this author inPubMed Google Scholar * U Kamasani View author

publications You can also search for this author inPubMed Google Scholar * G C Prendergast View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING

AUTHOR Correspondence to G C Prendergast. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Huang, M., Kamasani, U. & Prendergast, G. RhoB facilitates

c-Myc turnover by supporting efficient nuclear accumulation of GSK-3. _Oncogene_ 25, 1281–1289 (2006). https://doi.org/10.1038/sj.onc.1209174 Download citation * Received: 21 December 2004 *

Revised: 09 September 2005 * Accepted: 09 September 2005 * Published: 17 October 2005 * Issue Date: 02 March 2006 * DOI: https://doi.org/10.1038/sj.onc.1209174 SHARE THIS ARTICLE Anyone you

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Springer Nature SharedIt content-sharing initiative KEYWORDS * Ras * Rho * Akt * cancer