Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 8 March 2011
Vol. 4, Issue 163, p. ra13
[DOI: 10.1126/scisignal.2001518]


Editor's Summary

Ubiquitination for Activity
Mutational activation of the guanosine triphosphatase (GTPase) Ras occurs frequently in various cancers. Although the three mammalian isoforms—N-Ras, H-Ras, and K-Ras—couple to the same set of downstream signaling pathways, mutations in each isoform are associated with different types of cancers. In contrast to previous work showing that ubiquitination of N-Ras and H-Ras restricts their activity, Sasaki et al. found that monoubiquitination of Lys147 in K-Ras increased its activity and its ability to bind to downstream effector proteins. Cells expressing the oncogenic G12V mutant of Ras form tumors when injected into mice; however, cells expressing G12V Ras with an additional mutation abolishing ubiquitination of Lys147 formed smaller tumors in mice. Thus, cancers in which K-Ras activation drives tumor growth and survival could be targeted by treatments blocking K-Ras ubiquitination. The accompanying Perspective by Pfleger provides context on the distinct effects of ubiquitination on the abundance, activity, and access to effectors of different Ras isoforms.

Citation: A. T. Sasaki, A. Carracedo, J. W. Locasale, D. Anastasiou, K. Takeuchi, E. R. Kahoud, S. Haviv, J. M. Asara, P. P. Pandolfi, L. C. Cantley, Ubiquitination of K-Ras Enhances Activation and Facilitates Binding to Select Downstream Effectors. Sci. Signal. 4, ra13 (2011).

Read the Full Text

Phosphorylation at Ser-181 of Oncogenic KRAS Is Required for Tumor Growth.
C. Barcelo, N. Paco, M. Morell, B. Alvarez-Moya, N. Bota-Rabassedas, M. Jaumot, F. Vilardell, G. Capella, and N. Agell (2014)
Cancer Res. 74, 1190-1199
   Abstract »    Full Text »    PDF »
Degradation of Activated K-Ras Orthologue via K-Ras-specific Lysine Residues Is Required for Cytokinesis.
K. Sumita, H. Yoshino, M. Sasaki, N. Majd, E. R. Kahoud, H. Takahashi, K. Takeuchi, T. Kuroda, S. Lee, P. G. Charest, et al. (2014)
J. Biol. Chem. 289, 3950-3959
   Abstract »    Full Text »    PDF »
Ubiquitylation and activation of a Rab GTPase is promoted by a {beta}2AR-HACE1 complex.
V. Lachance, J. Degrandmaison, S. Marois, M. Robitaille, S. Genier, S. Nadeau, S. Angers, and J.-L. Parent (2014)
J. Cell Sci. 127, 111-123
   Abstract »    Full Text »    PDF »
Differences in the Regulation of K-Ras and H-Ras Isoforms by Monoubiquitination.
R. Baker, E. M. Wilkerson, K. Sumita, D. G. Isom, A. T. Sasaki, H. G. Dohlman, and S. L. Campbell (2013)
J. Biol. Chem. 288, 36856-36862
   Abstract »    Full Text »    PDF »
HDAC6 and SIRT2 Regulate the Acetylation State and Oncogenic Activity of Mutant K-RAS.
M. H. Yang, G. Laurent, A. S. Bause, R. Spang, N. German, M. C. Haigis, and K. M. Haigis (2013)
Mol. Cancer Res. 11, 1072-1077
   Abstract »    Full Text »    PDF »
4-Hydroxytamoxifen Induces Autophagic Death through K-Ras Degradation.
L. Kohli, N. Kaza, T. Coric, S. J. Byer, N. M. Brossier, B. J. Klocke, M.-A. Bjornsti, S. L. Carroll, and K. A. Roth (2013)
Cancer Res. 73, 4395-4405
   Abstract »    Full Text »    PDF »
Ubiquitin System: Direct Effects Join the Signaling.
A. L. Chernorudskiy and M. R. Gainullin (2013)
Science Signaling 6, pe22
   Abstract »    Full Text »    PDF »
Ras Protein/cAMP-dependent Protein Kinase Signaling Is Negatively Regulated by a Deubiquitinating Enzyme, Ubp3, in Yeast.
Y. Li and Y. Wang (2013)
J. Biol. Chem. 288, 11358-11365
   Abstract »    Full Text »    PDF »
Proteomic Analysis of Exosomes from Mutant KRAS Colon Cancer Cells Identifies Intercellular Transfer of Mutant KRAS.
M. Demory Beckler, J. N. Higginbotham, J. L. Franklin, A.-J. Ham, P. J. Halvey, I. E. Imasuen, C. Whitwell, M. Li, D. C. Liebler, and R. J. Coffey (2013)
Mol. Cell. Proteomics 12, 343-355
   Abstract »    Full Text »    PDF »
Regulation of RAS oncogenicity by acetylation.
M. H. Yang, S. Nickerson, E. T. Kim, C. Liot, G. Laurent, R. Spang, M. R. Philips, Y. Shan, D. E. Shaw, D. Bar-Sagi, et al. (2012)
PNAS 109, 10843-10848
   Abstract »    Full Text »    PDF »
Pheromone- and RSP5-dependent Ubiquitination of the G Protein {beta} Subunit Ste4 in Yeast.
M. Zhu, M. P. Torres, J. B. Kelley, H. G. Dohlman, and Y. Wang (2011)
J. Biol. Chem. 286, 27147-27155
   Abstract »    Full Text »    PDF »
Ubiquitin on Ras: Warden or Partner in Crime?.
C. M. Pfleger (2011)
Science Signaling 4, pe12
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882