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  • Original Paper
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Regulation of STAT protein synthesis by c-Cbl

Oncogene volume 20, pages 7326–7333 (2001)Cite this article

Abstract

Many cytokines and growth factors induce transcription of immediate early response genes by activating members of the Signal Transducers and Activators of Transcription (STAT) family. Although significant progress has been made in understanding the events that lead to the activation of STAT proteins, less is known about the regulation of their expression. Here we report that murine embryonic fibroblasts derived from c-Cbl-deficient mice display significantly increased levels of STAT1 and STAT5 protein. In contrast, STAT2 and STAT3 expression, as well as the levels of the tyrosine kinases Jak1 and Tyk2, appear to be regulated independently of c-Cbl. Interestingly, the half-life of STAT1 was unaffected by the presence of c-Cbl, indicating that c-Cbl acts independently of STAT1 degradation. Further analysis revealed similar levels of STAT1 mRNA, however, a dramatically increased rate of STAT1 protein synthesis was observed in c-Cbl-deficient cells. Thus, our findings demonstrate an additional control mechanism over STAT1 function, and also provide a novel biological effect of the Cbl protein family.

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Acknowledgements

We thank Konrad Miatkowski and Joe Amatucci for growing the murine IFNβ-expressing CHO cells, and Zhifang Li and Donna Hess for assaying the antiviral activity of the purified murine IFNβ. This work was supported in part by NIH grant CA80105. M David is a recipient of the Sidney Kimmel Foundation for Cancer Research Scholar Award.

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Authors and Affiliations

  1. Department of Biology and UCSD Cancer Center, University of California San Diego, La Jolla, California, USA

    Warren A Blesofsky, Kerri Mowen & Michael David

  2. Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, Melbourne, Australia

    Maria A Murphy & David D L Bowtell

  3. Biogen, Inc., Cambridge, Massachusetts, USA

    Robert M Arduini & Darren P Baker

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  1. Warren A Blesofsky
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  2. Kerri Mowen
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  3. Robert M Arduini
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  5. Maria A Murphy
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  6. David D L Bowtell
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  7. Michael David
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Correspondence to Michael David.

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Blesofsky, W., Mowen, K., Arduini, R. et al. Regulation of STAT protein synthesis by c-Cbl. Oncogene 20, 7326–7333 (2001). https://doi.org/10.1038/sj.onc.1204919

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