Subcellular distribution of Ras GTPase isoforms in normal human kidney

Kocher, Hemant M.; Senkus, Ron; Al-Nawab, M. D.; Hendry, Bruce M.

doi:10.1093/ndt/gfh744

Cited by 11 publications

(6 citation statements)

References 20 publications

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“…Subcellular localization of a protein often provides important clues to its function [20], and the transition from the benign state to the fully malignant one might involve a change in subcellular presence. As accumulating evidence has indicated that in many cancers the heterogeneous subcellular distribution and translocation of important cancer-related proteins, that is, Ras GTPase isoforms [21], cyclin D1 [22], p27 Kip1 [23], and chloride intracellular channel 4 [24], in tumor sites are associated with tumor characteristics and clinical outcome, and cause the loss and gain of function in essential activities, such changes are a new paradigm in sorting out changes that are relevant to malignant transformation. Thus, it would seem that alteration of the subcellular localization of ATG16L1 protein may contribute to the malignant phenotype of OSCC cells and could be a relevant event in oral carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Overexpression and altered subcellular localization of autophagy-related 16-like 1 in human oral squamous-cell carcinoma: correlation with lymphovascular invasion and lymph-node metastasis

et al. 2009

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Section: Discussionmentioning

confidence: 99%

Overexpression and altered subcellular localization of autophagy-related 16-like 1 in human oral squamous-cell carcinoma: correlation with lymphovascular invasion and lymph-node metastasis

et al. 2009

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“…Moreover, mutants in the RAS2 gene have been isolated as suppressors of mutants in genes encoding subunits of the mitochondrial ATP synthase (Mabuchi et al, 2000). Finally, it may be recalled that some reports of mitochondrial localization of Ras have been published, although their functional significance remains to be seen (Rebollo et al, 1999;Kocher et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Ras-dependent carbon metabolism and transformation in mouse fibroblasts

et al. 2006

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Mutational activation of ras genes is required for the onset and maintenance of different malignancies. Here we show, using a combination of molecular physiology, nutritional perturbations and transcriptional profiling, that full penetrance of phenotypes related to oncogenic Ras activation, including the shift of carbon metabolism towards fermentation and upregulation of key cell cycle regulators, is dependent upon glucose availability. These responses are induced by Ras activation, being specifically reverted by downregulation of the Ras pathway obtained through the expression of a dominant-negative Rasspecific guanine nucleotide exchange protein. Our data allow to link directly to ras activation the alteration in energy metabolism of cancer cells, their fragility towards glucose shortage and ensuing apoptotic death.

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“…In the human kidney, H-Ras localizes with mitochondria in proximal and distal convoluted tubules (30). Bcl-2 and Ras proteins interact at mitochondria in the murine T-cell line TS1␣ß, and the mitochondrial association of the three Ras proteins is differentially regulated by interleukin-2 supplementation (48).…”

Section: Discussionmentioning

confidence: 99%

Plasma Membrane Localization of Ras Requires Class C Vps Proteins and Functional Mitochondria in Saccharomyces cerevisiae

Wang

Deschenes

2006

Molecular and Cellular Biology

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Ras proteins are synthesized as cytosolic precursors, but then undergo posttranslational lipid addition, membrane association, and subcellular targeting to the plasma membrane. Although the enzymes responsible for farnesyl and palmitoyl lipid addition have been described, the mechanism by which these modifications contribute to the subcellular localization of Ras is not known. Following addition of the farnesyl group, Ras associates with the endoplasmic reticulum (ER), where palmitoylation occurs in Saccharomyces cerevisiae. The subsequent translocation of Ras from the ER to the plasma membrane does not require the classical secretory pathway or a functional Golgi apparatus. Vesicular and nonvesicular transport pathways for Ras proteins have been proposed, but the pathway is not known. Here we describe a genetic screen designed to identify mutants defective in Ras trafficking in S. cerevisiae. The screen implicates, for the first time, the class C VPS complex in Ras trafficking. Vps proteins are best characterized for their role in endosome and vacuole membrane fusion. However, the role of the class C Vps complex in Ras trafficking is distinct from its role in endosome and vacuole vesicle fusion, as a mitochondrial involvement was uncovered. Disruption of class C VPS genes results in mitochondrial defects and an accumulation of Ras proteins on mitochondrial membranes. Ras also fractionates with mitochondria in wild-type cells, where it is detected on the outer mitochondrial membrane by virtue of its sensitivity to protease treatment. These results point to a previously uncharacterized role of mitochondria in the subcellular trafficking of Ras proteins.

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Subcellular distribution of Ras GTPase isoforms in normal human kidney

Abstract: Ras isoforms have distinct and separate subcellular distributions in normal kidney cells. Understanding the functional aspects of this distribution pattern is essential if Ras is to be targeted by genetic or molecular therapeutic tools.

Cited by 11 publications

References 20 publications

Overexpression and altered subcellular localization of autophagy-related 16-like 1 in human oral squamous-cell carcinoma: correlation with lymphovascular invasion and lymph-node metastasis

Overexpression and altered subcellular localization of autophagy-related 16-like 1 in human oral squamous-cell carcinoma: correlation with lymphovascular invasion and lymph-node metastasis

Ras-dependent carbon metabolism and transformation in mouse fibroblasts

Plasma Membrane Localization of Ras Requires Class C Vps Proteins and Functional Mitochondria in Saccharomyces cerevisiae

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