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

• Published in: Oncogene Vol. 20; no. 51; pp. 7486 - 7493
• Main Authors: PAZ, Ariella, HAKLAI, Roni, ELAD-SFADIA, Galit, BALLAN, Eyal, KLOOG, Yoel
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 08.11.2001; Nature Publishing Group
• Subjects: Animals; Antisense RNA; Biological and medical sciences; Cell Division; Cell Membrane - metabolism; Cell Transformation, Neoplastic; DNA, Complementary - metabolism; Down-Regulation; farnesylthiosalycilic acid; Fluorescence; Fundamental and applied biological sciences. Psychology; Galectin 1; Genes, ras - genetics; Genetic transformation; Green fluorescent protein; Green Fluorescent Proteins; H-Ras protein; Hemagglutinins - metabolism; Humans; K-Ras protein; Lectins; Luminescent Proteins - metabolism; membrane anchorage; Microscopy, Confocal; Microscopy, Fluorescence; Mitogen-Activated Protein Kinases - metabolism; Molecular and cellular biology; Monomeric GTP-Binding Proteins - metabolism; Mutation; Oligonucleotides, Antisense - metabolism; Plasmids - metabolism; Protein Binding; Proteins; Ras protein; ras Proteins - metabolism; Rats; Signal transduction; Transfection; Tumors
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1204950

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.