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Molecular and Cellular Biology, May 2003, p. 3126-3140, Vol. 23, No. 9
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.9.3126-3140.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Cell Cycle Activation of the Swi6p Transcription Factor Is Linked to Nucleocytoplasmic Shuttling

Ethel Queralt and J. Carlos Igual*

Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de València, Burjassot, Spain

Received 6 December 2002/ Returned for modification 21 January 2003/ Accepted 6 February 2003

The control of the subcellular localization of cell cycle regulators has emerged as a crucial mechanism in the regulation of cell division. In the present work, we have characterized the function of the karyopherin Msn5p in the control of the cell cycle of Saccharomyces cerevisiae. Phenotypic analysis of the msn5 mutant revealed an increase in cell size and a functional interaction between Msn5p and the cell cycle transcription factor SBF (composed of the Swi4p and Swi6p proteins), indicating that Msn5p is involved in Start control. In fact, we have shown that the level of Cln2p protein is drastically reduced in an msn5 mutant. The effect on CLN2 expression is mediated at a transcriptional level, Msn5p being necessary for proper SBF-dependent transcription. On the contrary, loss of MSN5 has no effect on the closely related transcription factor MBF (composed of the Mbp1p and Swi6p proteins). Regulation of SBF by Msn5p is exerted by control of the localization of the regulatory subunit Swi6p. Swi6p shuttles between the nucleus and the cytoplasm during the cell cycle, and we have found that Msn5p is required for Swi6p export from the nucleus during the G2-M phase. What is more important, we have demonstrated that export of Swi6p to the cytoplasm is required for SBF activity, providing evidence for a functional switch of Swi6p linked to its nucleocytoplasmic shuttling during the cell cycle.

* Corresponding author. Mailing address: Dept. Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de València, C/Dr. Moliner 50, E-46100 Burjassot, Spain. Phone: (34)963543795. Fax: (34)963544635. E-mail: jcigual{at}uv.es.

Molecular and Cellular Biology, May 2003, p. 3126-3140, Vol. 23, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.9.3126-3140.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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