2014
DOI: 10.1073/pnas.1401727111
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NRAS isoforms differentially affect downstream pathways, cell growth, and cell transformation

Abstract: Significance The members of the rat sarcoma (RAS) gene family Kirsten rat sarcoma viral oncogene homolog, Harvey rat sarcoma viral oncogene homolog, and neuroblastoma RAS viral oncogene homolog (NRAS) belong to the most extensively studied oncogenes and are central players in carcinogenesis. Since their discovery approximately 30 y ago, efforts to target their aberrant activation have not led to major breakthroughs. We herein report the discovery of four so far undescribed variants of NRAS that diffe… Show more

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Cited by 29 publications
(38 citation statements)
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“…[4][5][6][7][8]11 with the activating NRAS mutation in the melanocytes, represent a metastatic melanoma model…”
Section: Accepted M Manuscriptmentioning
confidence: 99%
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“…[4][5][6][7][8]11 with the activating NRAS mutation in the melanocytes, represent a metastatic melanoma model…”
Section: Accepted M Manuscriptmentioning
confidence: 99%
“…The majority studied mutations occur primarily in the BRAF (a serine/threonine protein kinase) genes and have approved targeted therapies for patients in stage IV or unresectable melanoma. [4,5] However, newer emerging genetic targets include Neuroblastoma -Rat Sarcoma (NRAS) [4][5][6] and nuclear receptors like Retinoid X Receptor-α (RXRα) genes. [7,8] In pathological conditions, point mutations at the codon 61 of NRAS (NRASQ 61K ) gene locks the activated form of NRAS-GTP thereby promoting continuous up regulation of downstream effector proteins and signaling pathways in the malignant melanoma phenotype.…”
Section: Introductionmentioning
confidence: 99%
“…NRAS isoform 1 (or the canonical NRAS isoform) consists of exons 1-7 with an ORF spanning from exon 2-5, and produces a protein 189 amino acids in length (14). The additional four isoforms, as described in a previous publication arise from either the addition or deletion of exons (11). Isoform 2 contains an additional 57-bp-long exon downstream of exon 3 (named 3b by us) to produce a longer protein composed of 208 amino acids.…”
Section: Discussionmentioning
confidence: 99%
“…Notably, isoform 2 is the only variant with an additional, previously unknown exon, a property that may contribute to its altered role in melanoma. Interestingly, Eisfeld et al (11) found that overexpression of isoform 2 was able to enhance PI3K pathway signaling and decrease MAPK pathway signaling in COS-7 cells. This effect was also detected in the isoform 2 overexpressing A375 melanoma cell line in the present study.…”
Section: Discussionmentioning
confidence: 99%
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