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EMBO Rep. 2003 Aug;4(8):800-6. Epub 2003 Jul 11.

RAL GTPases are linchpin modulators of human tumour-cell proliferation and survival.

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  • 1Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9039, USA.


The monomeric RAL (RAS-like) GTPases have been indirectly implicated in mitogenic regulation and cell transformation. Here, we show that RALA and RALB collaborate to maintain tumorigenicity through regulation of both proliferation and survival. Remarkably, this task is divided between these highly homologous isoforms. RALB is specifically required for survival of tumour cells but not normal cells. RALA is dispensable for survival, but is required for anchorage-independent proliferation. Reducing the 'oncogenic burden' in human tumour cells relieves the sensitivity to loss of RALB. These observations establish RAL GTPases as crucial components of the cellular machinery that are exploited by factors that drive oncogenic transformation.

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