The forkhead protein Fkh2 is a component of the yeast cell cycle transcription factor SFF

Abstract

In the yeast Saccharomyces cerevisiae, the MADS-box protein Mcm1, which is highly related to mammalian SRF (serum response factor), forms a ternary complex with SFF (Swi five factor) to regulate the cell cycle expression of genes such as SWI5, CLB2 and ACE2. Here we show that the forkhead protein Fkh2 is a component of SFF and is essential for ternary complex formation on the SWI5 and ACE2 promoters. Fkh2 is essential for the correct cell cycle periodicity of SWI5 and CLB2 gene expression and is phosphorylated with a timing that is consistent with a role in this expression. Furthermore, investigation of the relationship between Fkh2 and a related forkhead protein Fkh1 demonstrates that these proteins act in overlapping pathways to regulate cell morphology and cell separation. This is the first example of a eukaryotic transcription factor complex containing both a MADS-box and a forkhead protein, and it has important implications for the regulation of mammalian gene expression.

A Systematic Screen for Transcriptional Regulators of the Yeast Cell Cycle

“…Deletion of Fkh1 and Fkh2, Ace2, Swi5, or various cell separation genes leads to inhibited cell separation, resulting in filamentous growth phenotypes similar to the overexpression phenotype of Sfg1 (Kovacech et al 1996;King and Butler 1998;Pan and Heitman 2000;Pic et al 2000;Zhu et al 2000;Bidlingmaier et al 2001;Doolin et al 2001;Fujita et al 2004Fujita et al , 2005. Furthermore, inappropriate activation of cell separation genes in the Dsfg1 strain is consistent with the finding that an sfg1 mutant is defective in filamentous growth, since cells must remain attached in this growth mode (Fujita et al 2005).…”

Disruption of Yeast Forkhead-associated Cell Cycle Transcription by Oxidative Stress

“…This resulted in the identification of two additional genes in the G2/M cluster, not reported in Zhu et al (2000) encoding a putative integral membrane protein, Sur7p, and an RNA-binding and localizing protein, Hek2p, suggesting that they may have roles in cell cycle FKH-regulated processes. HEK2 was previously reported as FKH regulated (Pic et al, 2000). Further examination of the G1 cluster in Figure 5 similarly implicated a few additional genes: GIC2, encoding a small GTPase-interacting protein that localizes to the incipient bud site; RME1, encoding a transcription regulator that is regulated by Swi5p ; SHQ1, a gene important for small nucleolar ribonucleoprotein particles stability; and YJL217W, encoding a hypothetical protein.…”

“…The major part of this coordination is achieved by the sequential activation of a small number of transcription regulators (reviewed in Mendenhall and Hodge, 1998): MBF (a complex of Mbp1p and Swi6p) and SBF (a complex of Swi4p and Swi6p) are responsible for activating G1 transcription (Koch et al, 1993); Fkh1p and a complex formed by the cooperative promoter binding of Mcm1p and Fkh2p and a later recruitment of Ndd1p are responsible for activating G2/M transcription (Koranda et al, 2000;Kumar et al, 2000;Pic et al, 2000;Hollenhorst et al, 2001); Swi5p and Ace2p, which are themselves expressed during G2/M, are the transcription factors responsible for activating the greater part of the next wave of M/G1 transcription (Dohrmann et al, 1992;Toyn et al, 1997); and Mcm1p, this time alone, is additionally responsible for activating transcription of several other M/G1 genes (McInerny et al, 1997).…”

Degradation of Ndd1 by APC/CCdh1 generates a feed forward loop that times mitotic protein accumulation

“…1b). Ndd1 is the activator of the Mcm1-Fkh2 transcription factor complex [21][22][23][24] . The protein levels of Ndd1 oscillate periodically and it has been previously speculated 28 that it might be degraded by the APC/C.…”

“…We thus set up an unbiased screen designed to probe the entire yeast proteome. During the pilot stage of this screen, we identified Ndd1, an essential protein, which activates the Mcm1-Fkh2 G2-specific transcription factor [21][22][23][24] . We show here that Ndd1 is an APC/C Cdh1 substrate and that the APC/C Cdh1 is a major regulator of the cell cycle-specific oscillations of Ndd1.…”