This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Villalonga, P.
Right arrow Articles by Ridley, A. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Villalonga, P.
Right arrow Articles by Ridley, A. J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2004, p. 7829-7840, Vol. 24, No. 18
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.18.7829-7840.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

RhoE Inhibits Cell Cycle Progression and Ras-Induced Transformation

Priam Villalonga,1 Rosa M. Guasch,1,{dagger} Kirsi Riento,1 and Anne J. Ridley1,2*

Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine,1 Department of Biochemistry and Molecular Biology, University College London, London, United Kingdom2

Received 26 February 2004/ Returned for modification 26 March 2004/ Accepted 21 June 2004

Rho GTPases are major regulators of cytoskeletal dynamics, but they also affect cell proliferation, transformation, and oncogenesis. RhoE, a member of the Rnd subfamily that does not detectably hydrolyze GTP, inhibits RhoA/ROCK signaling to promote actin stress fiber and focal adhesion disassembly. We have generated fibroblasts with inducible RhoE expression to investigate the role of RhoE in cell proliferation. RhoE expression induced a loss of stress fibers and cell rounding, but these effects were only transient. RhoE induction inhibited cell proliferation and serum-induced S-phase entry. Neither ROCK nor RhoA inhibition accounted for this response. Consistent with its inhibitory effect on cell cycle progression, RhoE expression was induced by cisplatin, a DNA damage-inducing agent. RhoE-expressing cells failed to accumulate cyclin D1 or p21cip1 protein or to activate E2F-regulated genes in response to serum, although ERK, PI3-K/Akt, FAK, Rac, and cyclin D1 transcription was activated normally. The expression of proteins that bypass the retinoblastoma (pRb) family cell cycle checkpoint, including human papillomavirus E7, adenovirus E1A, and cyclin E, rescued cell cycle progression in RhoE-expressing cells. RhoE also inhibited Ras- and Raf-induced fibroblast transformation. These results indicate that RhoE inhibits cell cycle progression upstream of the pRb checkpoint.

* Corresponding author. Mailing address: Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, 91 Riding House St., London W1W 7BS, United Kingdom. Phone: 44 20 7878 4033. Fax: 44 20 7878 4040. E-mail: anne{at}ludwig.ucl.ac.uk.

{dagger} Present address: Instituto de Investigaciones Citologicas (FVIB), 46010 Valencia, Spain.

Molecular and Cellular Biology, September 2004, p. 7829-7840, Vol. 24, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.18.7829-7840.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Klein, R. M., Aplin, A. E. (2009). Rnd3 Regulation of the Actin Cytoskeleton Promotes Melanoma Migration and Invasive Outgrowth in Three Dimensions. Cancer Res. 69: 2224-2233 [Abstract] [Full Text]  
  • Liebig, T., Erasmus, J., Kalaji, R., Davies, D., Loirand, G., Ridley, A., Braga, V. M.M. (2009). RhoE Is Required for Keratinocyte Differentiation and Stratification. Mol. Biol. Cell 20: 452-463 [Abstract] [Full Text]  
  • Wang, J., Chen, L., Li, P., Li, X., Zhou, H., Wang, F., Li, D., Yin, Y., Wu, G. (2008). Gene Expression Is Altered in Piglet Small Intestine by Weaning and Dietary Glutamine Supplementation. J. Nutr. 138: 1025-1032 [Abstract] [Full Text]  
  • Klein, R. M., Spofford, L. S., Abel, E. V., Ortiz, A., Aplin, A. E. (2008). B-RAF Regulation of Rnd3 Participates in Actin Cytoskeletal and Focal Adhesion Organization. Mol. Biol. Cell 19: 498-508 [Abstract] [Full Text]  
  • Hatzoglou, A., Ader, I., Splingard, A., Flanders, J., Saade, E., Leroy, I., Traver, S., Aresta, S., de Gunzburg, J. (2007). Gem Associates with Ezrin and Acts via the Rho-GAP Protein Gmip to Down-Regulate the Rho Pathway. Mol. Biol. Cell 18: 1242-1252 [Abstract] [Full Text]  
  • Boswell, S. A., Ongusaha, P. P., Nghiem, P., Lee, S. W. (2007). The Protective Role of a Small GTPase RhoE against UVB-induced DNA Damage in Keratinocytes. J. Biol. Chem. 282: 4850-4858 [Abstract] [Full Text]  
  • Lartey, J., Gampel, A., Pawade, J., Mellor, H., Bernal, A. L. (2006). Expression of RND Proteins in Human Myometrium. Biol. Reprod. 75: 452-461 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»