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Ral-GTPases: good chances for a long-lasting fame

Oncogene volume 24, pages 326–328 (2005)Cite this article

Oncogenic constitutively active RAS mutants are found in 30% of all human cancers. In addition to acquisition of point mutations, functional activation of RAS may occur as a part of altered intracellular signal transduction associated with oncogenic transformation. Since RAS appears as a common signal transduction crossroad for various regulatory pathways, there is hardly an aspect of malignant phenotype that was not described as being affected by its activation (reviewed in Malumbres and Barbacid, 2003; and in Campbell and Der, 2004).

Pleiotropic oncogenic properties of RAS are materialized through interaction with multiple downstream effector proteins, which, in turn, also have a solid established role in tumorigenesis. RAS–RAF interaction leads to the activation of RAF kinase and subsequent triggering of MEK-ERK cascade. RAS–PI3K interaction stimulates lipid kinase activity of the latter, resulting in the activation of a network of downstream effectors, which include AKT S6 kinase, several isoforms of PKC and RAC-GEFs. Binding of RAS to the proteins known as RAL-GEFs (RAL GDS, RGL1 and 2, RLF) triggers activation of RAS-related subfamily of small GTPases consisting of two homologous proteins, RAL-A and -B. Molecular mechanisms that imply RAL-mediated signaling in tumorigenesis are the least characterized compared to enormous amount of data accumulated on cancer connection of MEK/ERK and PI3K pathways. Nevertheless, recent works unequivocally indicate that contribution of RAL to the pathogenesis of cancer, in general, and to RAS-dependent cancerogenesis, specifically, was probably underestimated. It is, therefore, understandable why a fresh and comprehensive review by Feig (2003) on RAL-dependent signaling was entitled: ‘Ral-GTPases: approaching their 15 min of fame’. In light of this, an elegant study by the Moscow (Russia) group led by A. TatosyanFootnote 1 (Tchevkina et al., 2004), which establishes a unique role of RAL-A in RAS-mediated metastasis, has appeared just in time.

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Notes

  1. Deceased on 05∣06∣04.

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  1. Quark Biotech Inc., Ness Ziona, Israel

    Elena Feinstein

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  1. Elena Feinstein
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Correspondence to Elena Feinstein.

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Feinstein, E. Ral-GTPases: good chances for a long-lasting fame. Oncogene 24, 326–328 (2005). https://doi.org/10.1038/sj.onc.1208252

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