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Phosphorylation of MCT-1 by p44/42 MAPK is required for its stabilization in response to DNA damage

Oncogene volume 26, pages 2283–2289 (2007)Cite this article

A Corrigendum to this article was published on 19 April 2007

Abstract

We discovered a novel oncogene in a T-cell lymphoma cell line, multiple copies in T-cell lymphoma-1 (MCT-1), that has been shown to decrease cell-doubling time, shorten the duration of G1 transit time and/or G1-S transition, and transform NIH3T3 fibroblasts. We subsequently demonstrated that there were significantly increased levels of MCT-1 protein in a subset of primary diffuse large B-cell lymphomas. Levels of MCT-1 protein were shown to be increased after exposure to DNA damaging agents. This increase did not require new protein synthesis, suggesting that post-translational mechanisms were involved. Phosphorylation is one potential mechanism by which the activity of molecules involved in cell cycle/survival is rapidly modulated. The RAS/mitogen-activated/extracellular-regulated kinase (MEK)/extracellular signal-regulated kinases (ERK) pathway plays a prominent role in the regulation of cell growth and proliferation through phosphorylation-dependent regulation of several substrates. The MCT-1 protein is predicted to have numerous putative phosphorylation sites. Using a combination of genetic and pharmacological approaches, we established that phosphorylation of MCT-1 protein by p44/p42 mitogen-activated protein kinases is critical for stabilization of MCT-1 protein and for its ability to promote cell proliferation. Our data suggests that targeting the RAS/MEK/ERK signal transduction cascade may provide a potential therapeutic approach in lymphomas and related malignancies that exhibit high levels of MCT-1 protein.

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Authors and Affiliations

  1. Department of Medicine, University of California, San Diego, La Jolla, CA, USA

    S Nandi

  2. University of Maryland Greenebaum Cancer Center, Baltimore, MD, USA

    L S Reinert, A Hachem, K Mazan-Mamczarz, P Hagner, H He & R B Gartenhaus

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  1. S Nandi
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  2. L S Reinert
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  3. A Hachem
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  4. K Mazan-Mamczarz
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  5. P Hagner
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  6. H He
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  7. R B Gartenhaus
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Correspondence to R B Gartenhaus.

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Nandi, S., Reinert, L., Hachem, A. et al. Phosphorylation of MCT-1 by p44/42 MAPK is required for its stabilization in response to DNA damage. Oncogene 26, 2283–2289 (2007). https://doi.org/10.1038/sj.onc.1210030

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