The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
V600E BRAF is associated with disabled feedback inhibition of RAF–MEK signaling and elevated transcriptional output of the pathway
Open accessAbstract
Tumors with mutant BRAF and those with receptor tyrosine kinase (RTK) activation have similar levels of phosphorylated ERK, but only the former depend on ERK signaling for proliferation. The mitogen-activated protein kinase, extracellular signal-regulated kinase kinase (MEK)/ERK-dependent transcriptional output was defined as the genes whose expression changes significantly 8 h after MEK inhibition. In V600E BRAF cells, this output is comprised of 52 genes, including transcription factors that regulate transformation and members of the dual specificity phosphatase and Sprouty gene families, feedback inhibitors of ERK signaling. No such genes were identified in RTK tumor cells, suggesting that ERK pathway signaling output is selectively activated in BRAF mutant tumors. We find that RAF signaling is feedback down-regulated in RTK cells, but is insensitive to this feedback in BRAF mutant tumors. Physiologic feedback inhibition of RAF/MEK signaling down-regulates ERK output in RTK cells; evasion of this feedback in mutant BRAF cells is associated with increased transcriptional output and MEK/ERK-dependent transformation.
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Self-citationTargeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies
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The role of BRAF V600 mutation in melanoma
Ascierto, P. A., Kirkwood, J. M., Grob, J.-J., Simeone, E., Grimaldi, A. M., Maio, M., Palmieri, G., Testori, A., Marincola, F. M., & Mozzillo, N. (2012) · Journal of Translational Medicine · doi:10.1186/1479-5876-10-85 · Cited by 801
Metadata
- Authors
- Pratilas, C. A., Taylor, B. S., Ye, Q., Viale, A., Sander, C., Solit, D. B., & Rosen, N.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-03-17
- Volume
- 106
- Issue
- 11
- Pages
- 4519-4524
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2038683568
- Cited by
- 614
- References
- 45
- FWCI
- 15.48
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Pratilas, C. A., Taylor, B. S., Ye, Q., Viale, A., Sander, C., Solit, D. B., & Rosen, N. (2009). V600E BRAF is associated with disabled feedback inhibition of RAF–MEK signaling and elevated transcriptional output of the pathway. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0900780106
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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