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Galectin-1 binds oncogenic H-Ras to mediate Ras membrane anchorage and cell transformation

Oncogene volume 20, pages 7486–7493 (2001)Cite this article

Abstract

Ras genes, frequently mutated in human tumors, promote malignant transformation. Ras transformation requires membrane anchorage, which is promoted by Ras farnesylcysteine carboxymethylester and by a second signal. Previously we showed that the farnesylcysteine mimetic, farnesylthiosalicylic acid (FTS) disrupts Ras membrane anchorage. To understand how this disruption contributes to inhibition of cell transformation we searched for new Ras-interacting proteins and identified galectin-1, a lectin implicated in human tumors, as a selective binding partner of oncogenic H-Ras(12V). The observed size of H-Ras(12V)-galectin-1 complex, which is equal to the sum of the molecular weights of Ras and galectin-1 indicates a direct binding interaction between the two proteins. FTS disrupted H-Ras(12V)-galectin-1 interactions. Overexpression of galectin-1 increased membrane-associated Ras, Ras-GTP, and active ERK resulting in cell transformation, which was blocked by dominant negative Ras. Galectin-1 antisense RNA inhibited transformation by H-Ras(12V) and abolished membrane anchorage of green fluorescent protein (GFP)-H-Ras(12V) but not of GFP-H-Ras wild-type (wt), GFP-K-Ras(12V), or GFP-N-Ras(13V). H-Ras(12V)-galectin-1 interactions establish an essential link between two proteins associated with cell transformation and human malignancies that can be exploited to selectively target oncogenic Ras proteins.

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Acknowledgements

We thank A Admon for sequence analysis, HJ Gabius and K Yamaoka for galectin-1 antibodies, J Boss for the Ras-RBD assay, and S Smith for editorial assistance. This work was supported in part by Grant no. 97000141 from the U.S.–Israel Binational Science Foundation, by the Israel Cancer Foundation, and by the Austrian Friends of Tel-Aviv University.

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Authors and Affiliations

  1. Department of Neurobiochemistry, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, 69978, Israel

    Ariella Paz, Roni Haklai, Galit Elad-Sfadia, Eyal Ballan & Yoel Kloog

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  1. Ariella Paz
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  2. Roni Haklai
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Correspondence to Yoel Kloog.

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Paz, A., Haklai, R., Elad-Sfadia, G. et al. Galectin-1 binds oncogenic H-Ras to mediate Ras membrane anchorage and cell transformation. Oncogene 20, 7486–7493 (2001). https://doi.org/10.1038/sj.onc.1204950

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