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Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan

Address correspondence to Akio Toh-e, Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan. Tel.: 81-3-5684-9420. Fax: 81-3-5841-4465. E-mail: toh-e{at}biol.s.u-tokyo.ac.jp

ACdc25 family protein Lte1 (low temperature essential) is essential for mitotic exit at a lowered temperature and has been presumed to be a guanine nucleotide exchange factor (GEF) for a small GTPase Tem1, which is a key regulator of mitotic exit. We found that Lte1 physically associates with Ras2-GTP both in vivo and in vitro and that the Cdc25 homology domain (CHD) of Lte1 is essential for the interaction with Ras2. Furthermore, we found that the proper localization of Lte1 to the bud cortex is dependent on active Ras and that the overexpression of a derivative of Lte1 without the CHD suppresses defects in mitotic exit of a lte1 mutant and a ras1 ras2 mutant. These results suggest that Lte1 is a downstream effector protein of Ras in mitotic exit and that the Ras GEF domain of Lte1 is not essential for mitotic exit but required for its localization.

Key Words: cell cycle; mitotic exit; Lte1; Ras; budding yeast

^* Abbreviations used in this paper: CHD, Cdc25 homology domain; GEF, guanine nucleotide exchange factor; PKA, protein kinase A.

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