Mizunuma M, Tsubakiyama R, Ogawa T, Shitamukai A, Kobayashi Y, Inai T, Kume K, Hirata D

The Start/G1 phase in the cell cycle is an important period during which cells determine the fate, onset of mitotic progression or the switch to developmental stages in response to both external and internal signals. In the budding yeast Saccharomyces cerevisiae, Whi3, a negative regulator of the G1 cyclins, has ...

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been identified as a positive regulator of cell-size control and is involved in the regulation of Start. However, the regulatory pathway of Whi3 governing the response to multiple signals remains largely unknown. Here we show that Whi3 was phosphorylated by the RAS/cAMP-dependent protein kinase (PKA) and that the phosphorylation of Ser-568 in Whi3 by PKA played an inhibitory role in the Whi3 function. Phosphorylation of Whi3 by PKA led to decreased interaction of it with CLN3 G1 cyclin mRNA and was required for the promotion of the G1/S progression. Further, we demonstrate that the phospho-mimetic S568D mutation of Whi3 prevented the developmental fate switch to sporulation or invasive growth. Thus, PKA modulated the function of Whi3 by phosphorylation, thus implicating PKA-mediated modulation of Whi3 in multiple cellular events.

Date: Mar. 07, 2013

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