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Inactivation of Ras function by allele-specific peptide aptamers

Oncogene volume 21, pages 5753–5757 (2002)Cite this article

Abstract

One challenge facing biology is the elucidation of the function of the estimated 30 000 human genes and their polymorphic variants. Reagents that affect the activity of specific genes will be useful in the dissection of cellular regulatory networks. Here, as a test case, we used a two-bait two-hybrid system to identify peptide aptamers that distinguish allelic forms of H-Ras. Some of these anti-Ras aptamters inhibit the interaction of oncogenic Ras with c-Raf1 in vitro, and abolish EGF-stimulated activation of c-Raf1 in vivo. These experiments show that the inactivation of protein function by peptide aptamers represents a viable approach to the understanding and control of signaling pathways and oncogenic missense alleles.

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Acknowledgements

C Wilson Xu is grateful to Roger Brent for his enthusiastic support and guidance and for allowing us to publish this work that was mostly completed in his laboratory. We thank Joseph Avruch for his help with the c-Raf1 kinase assays The work was supported in part by the American Cancer Society (CW Xu) and NIH grant GM57959 (Z Luo).

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Authors and Affiliations

  1. Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10021, NY, USA

    C Wilson Xu

  2. Department of Medicine, Diabetes and Metabolism Unit, Boston University School of Medicine, 88 East Newton Street, Boston, 02118, Massachusetts, MA, USA

    Zhijun Luo

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  1. C Wilson Xu
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Correspondence to C Wilson Xu.

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Xu, C., Luo, Z. Inactivation of Ras function by allele-specific peptide aptamers. Oncogene 21, 5753–5757 (2002). https://doi.org/10.1038/sj.onc.1205680

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