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

A. Paz, R. Haklai, G. Elad-Sfadia, E. Ballan, Y. Kloog*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

349 Scopus citations

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.

Original languageEnglish
Pages (from-to)7486-7493
Number of pages8
JournalOncogene
Volume20
Issue number51
DOIs
StatePublished - 8 Nov 2001

Funding

FundersFunder number
Austrian Friends of Tel-Aviv University
Israel Cancer Foundation
U.S. – Israel Binational Science Foundation

    Keywords

    • Cell transformation
    • Galectin-1
    • Oncogenic Ras
    • Ras localization

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