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Feedback regulation of the MBF transcription factor by cyclin Cig2

Nature Cell Biology volume 3, pages 1043–1050 (2001)Cite this article

Abstract

The Mlu1-binding factor (MBF) from the fission yeast Schizosaccharomyces pombe contains the proteins Res1p and Res2p and binds to the Mlu1 cell-cycle box (MCB) element in DNA, activating the transcription of genes required for S phase. We report here that the cell-cycle-regulated expression of the cyclin cig2 gene is dependent on MBF. Deletion of MCB elements in the cig2 promoter perturbed the expression not only of cig2 but also of other MBF-dependent genes, indicating that Cig2p could regulate MBF activity. Cig2p can bind to Res2p, promote the phosphorylation of Res1p and inhibit MBF-dependent gene transcription. Cig2p thus forms an autoregulating feedback-inhibition loop with MBF which is important for normal regulation of the cell cycle.

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Figure 1: cig2 expression is dependent on MCB promoter elements.
Figure 2: Disruption of the cig2 promoter.
Figure 3: Cig2p binds to the N terminus of Res2p.
Figure 4: Cig2p-dependent phosphorylation of Res1p.
Figure 5: Res1-S130A rescues the lethal haploid meiosis of pat1-114.
Figure 6: Effect of Res1-S130A on MBF-dependent transcription.
Figure 7: Cig2p inhibits the transcription of MBF-dependent genes.
Figure 8: Model of the negative feedback loop of Cig2p on MBF-dependent transcription.

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Acknowledgements

We thank H. Okayama, S. Moreno and T. Enoch for providing S. pombe strains and plasmids, S. Dalal for critically reading the manuscript, and members of the DeCaprio and Nurse laboratories for helpful suggestions and comments. We thank J. Gan for preparation of monoclonal antibodies. J.A.thanks Elena Hidalgo at Universitat Pompeu Fabra, where some of this work was performed. J.A. was supported by a Fellowship from the Generalitat de Catalunya (CIRIT) and Marie Curie TMR. J.A.D. is a Scholar of the Leukemia and Lymphoma Society. Part of this work was supported by a grant to Elena Hidalgo from Dirección General de Investigación, Spain.

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Authors and Affiliations

  1. Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney St, Boston, 02115, Massachusetts, USA

    José Ayté, Colleen Schweitzer & James A. DeCaprio

  2. Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

    José Ayté, Patrick Zarzov & Paul Nurse

  3. Department de Ciències Experimentals i de la Salut, Cell Signalling Unit, Universitat Pompeu Fabra, C Doctor Aiguader 80, Barcelona, 08003, Spain

    José Ayté

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Correspondence to James A. DeCaprio.

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Figure S1 Extracts from wild type strain (2 mg) were immunoprecipitated with the indicated monoclonal antibodies (IP Ab). (PDF 68 kb)

Figure S2 FACS analysis corresponding to Figure 4D.

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Ayté, J., Schweitzer, C., Zarzov, P. et al. Feedback regulation of the MBF transcription factor by cyclin Cig2. Nat Cell Biol 3, 1043–1050 (2001). https://doi.org/10.1038/ncb1201-1043

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