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Early G1 growth arrest of hybridoma B cells by DMSO involves cyclin D2 inhibition and p21[CIP1] induction

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Abstract

Dimethylsulfoxide (DMSO) was shown to inhibit the proliferation of several B cell lines including Raji, Daudi, and SKW6-CL4 but the mechanisms involved in this growth arrest are still unclear. We show that in 7TD1 mouse hybridoma cells a DMSO-induced reversible G1 arrest involves inactivation of Rb kinases, cyclin D2/CDK4 and cyclin E/CDK2. This occurs by at least three distinct mechanisms. Inhibition of cyclin D2 neosynthesis leads to a dramatic decrease of cyclinD2/CDK4 complexes. This in turn enables the redistribution of p27[KIP1] from cyclin D2/CDK4 to cyclin E/CDK2 complexes. In addition, the simultaneous accumulation of p21[CIP1] entails increasing association with cyclin D3/CDK4 and cyclin E/CDK2. Thus, p21[CIP1] and p27[KIP1], act in concert to inhibit cyclin E/CDK2 activity which, together with CDK4 inactivation, confers a G1-phase arrest.

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Authors and Affiliations

  1. INSERM U364, Faculté de Médecine, avenue de Valombrose, Nice, Cedex 02, 06107, France

    Gilles Ponzio, Agnès Loubat, Nathalie Rochet, Laurent Turchi, Dariush Farahi Far & Bernard Rossi

  2. Laboratoire d'Immunologie Clinique, Hopital Cantonal de Genève, 24, Rue Micheli-du Crest, CH-1211, Genève, 14, Switzerland

    Roger Rezzonico

  3. CRBM (CNRS) ERS 155, 1919 route de Mende, Montpellier, 34033, France

    Vjekoslav Dulic

Authors
  1. Gilles Ponzio
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  2. Agnès Loubat
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  3. Nathalie Rochet
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  4. Laurent Turchi
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  5. Roger Rezzonico
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  6. Dariush Farahi Far
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  7. Vjekoslav Dulic
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  8. Bernard Rossi
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Ponzio, G., Loubat, A., Rochet, N. et al. Early G1 growth arrest of hybridoma B cells by DMSO involves cyclin D2 inhibition and p21[CIP1] induction. Oncogene 17, 1159–1166 (1998). https://doi.org/10.1038/sj.onc.1202040

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  • DOI: https://doi.org/10.1038/sj.onc.1202040

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