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P38SAPK2 phosphorylates cyclin D3 at Thr-283 and targets it for proteasomal degradation

Oncogene volume 23, pages 7537–7544 (2004)Cite this article

Abstract

Cyclin D3 plays a critical role in maturation of precursor T cells and their levels are tightly regulated during this process. Alteration of cyclin D3 levels has been proposed to be important in the development of different human cancers, including malignancies of the lymphoid system. Thus, we have analysed the mechanisms involved in the regulation of cyclin D3 levels. Our results indicate that cyclin D3 is degraded via proteasome and that Thr-283 is essential for its degradation. Wild-type cyclin D3 but not the Thr-283A mutant accumulated ubiquitylated forms after treatment with proteasome inhibitors. We also observed that different type of stresses promote the Thr-283-dependent in vivo degradation of cyclin D3. The analysis of the kinases involved in Thr-283 phosphorylation indicates that all the members of the p38SAPK family of serine–threonine kinases are able to phosphorylate cyclin D3 at this specific site. Moreover, we found that the overexpression of p38αSAPK2 induce the decrease of cyclin D3 in vivo. These results indicate that p38SAPK might be involved in the regulation of cyclin D3 levels and suggest that this mechanism is involved in the maturation of precursor T-cells. Alterations of this mechanism might be important for oncogenesis.

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Acknowledgements

We thank René H Medema from the Netherlands Cancer Institute, Amsterdam, for kindly providing the Jurkat-D3II cell line. This work was supported by Grants, SAF 2000-0052, SAF2002-00452, and SAF2003-08339 from the Ministerio de Ciencia y Tecnología from Spain.

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  1. Oriol Casanovas and Montserrat Jaumot: Both authors contributed equally to this work

Authors and Affiliations

  1. Departament de Biologia Cel lular i Anatomia Patològica, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Casanova 143, Barcelona, 08036, Spain

    Oriol Casanovas, Montserrat Jaumot, Ana-Belén Paules, Neus Agell & Oriol Bachs

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  1. Oriol Casanovas
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  2. Montserrat Jaumot
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Correspondence to Oriol Bachs.

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Casanovas, O., Jaumot, M., Paules, AB. et al. P38SAPK2 phosphorylates cyclin D3 at Thr-283 and targets it for proteasomal degradation. Oncogene 23, 7537–7544 (2004). https://doi.org/10.1038/sj.onc.1208040

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