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EMBO reports 4, 8, 800–806 (2003)
doi:10.1038/sj.embor.embor899
AOP Published online: 11 July 2003
RAL GTPases are linchpin modulators of human tumour-cell proliferation and survival
Yuchen Chien & Michael A. White
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Department of Cell Biology, University of Texas
Southwestern Medical Center, 5323 Harry Hines Boulevard,
Dallas, Texas 75390-9039, USA
To whom correspondence should be addressed
Michael A. White Tel: +1 214 648 2861; Fax: +1 214 648 8694;
michael.white@utsouthwestern.edu
Received 2 January 2003; Accepted 12 June 2003; Published online 11 July 2003.
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Abstract
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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