The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCKα kinases
Open accessAbstract
Little is known about the regulation and function of the Notch1 gene in negative control of human tumors. Here we show that Notch1 gene expression and activity are substantially down-modulated in keratinocyte cancer cell lines and tumors, with expression of this gene being under p53 control in these cells. Genetic suppression of Notch signaling in primary human keratinocytes is sufficient, together with activated ras, to cause aggressive squamous cell carcinoma formation. Similar tumor-promoting effects are also caused by in vivo treatment of mice, grafted with keratinocytes expressing oncogenic ras alone, with a pharmacological inhibitor of endogenous Notch signaling. These effects are linked with a lesser commitment of keratinocytes to differentiation, an expansion of stem cell populations, and a mechanism involving up-regulation of ROCK1/2 and MRCKα kinases, two key effectors of small Rho GTPases previously implicated in neoplastic progression. Thus, the Notch1 gene is a p53 target with a role in human tumor suppression through negative regulation of Rho effectors.
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Cites
In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2
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RHO GTPASES: Biochemistry and Biology
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Metadata
- Authors
- Lefort, K., Mandinova, A., Ostano, P., Kolev, V., Calpini, V., Kolfschoten, I., Devgan, V., Lieb, J., Raffoul, W., Hohl, D., Neel, V., Garlick, J., Chiorino, G., & Dotto, G. P.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2007-03-01
- Volume
- 21
- Issue
- 5
- Pages
- 562-577
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2153558905
- Cited by
- 305
- References
- 6
- Type
- posted content
- Language
- en
- Open access
- diamond
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- CoChat. (2026). Citation check: Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCKα kinases. https://app.cochat.ai/papers/10.1101/gad.1484707
- The paper
- Lefort, K., Mandinova, A., Ostano, P., Kolev, V., Calpini, V., Kolfschoten, I., Devgan, V., Lieb, J., Raffoul, W., Hohl, D., Neel, V., Garlick, J., Chiorino, G., & Dotto, G. P. (2007). Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCKα kinases. Genes & Development. https://doi.org/10.1101/gad.1484707
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