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Gene Review

FKH2  -  Fkh2p

Saccharomyces cerevisiae S288c

Synonyms: Fork head protein homolog 2, N2403, YNL068C, YNL2403C
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High impact information on FKH2

  • Finally, the fkh1 fkh2 mutant displays a constitutive pseudohyphal morphology, indicating that Fkh1 and Fkh2 may help control the switch to this mode of growth [1].
  • Its recruitment depends on a permanent protein-DNA complex consisting of the MADS box protein, Mcm1, and a recently identified partner Fkh2, a forkhead/winged helix related transcription factor [2].
  • Although an essential gene, NDD1 is dispensable in cells expressing a truncated form of Fkh2p lacking its C terminus [3].
  • Activation of the CLB gene cluster through the assembly of Mcm1p-Fkh2p complexes at target promoters is essential for mitotic entry and transition through M phase [3].
  • Recruitment of Thr 319-phosphorylated Ndd1p to the FHA domain of Fkh2p requires Clb kinase activity: a mechanism for CLB cluster gene activation [3].

Biological context of FKH2


Physical interactions of FKH2

  • 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 [8].
  • The forkhead transcription factor Fkh2p acts in a DNA-bound complex with Mcm1p and the coactivator Ndd1p to regulate cell cycle-dependent expression of the CLB2 gene cluster in Saccharomyces cerevisiae [9].

Regulatory relationships of FKH2

  • These phosphorylation-dependent changes in the Fkh2p-Ndd1p complex play an important role in the cell cycle-regulated expression of the CLB2 cluster [9].
  • However, phosphorylation of a cofactor, Ndd1, by Cdk1 late in the cell cycle promotes binding to Fkh2 and conversion into a transcriptional activator [10].

Other interactions of FKH2

  • Interestingly, deletions in either FKH1 or FKH2 alone caused subtle but opposite effects on cell-cycle progression and CLB2 mRNA expression, consistent with a role for each of these genes in modulating the cell cycle and having opposing effects on silencing [4].
  • 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 [8].
  • Ndd1p was found to be phosphorylated in a cell cycle-dependent manner by Cdc28p-Clb2p, and, importantly, this phosphorylation event promotes interactions between Ndd1p and the FHA domain of Fkh2p [11].
  • Occasionally, multiseptate cells were also produced, indicating the involvement of fhl1 and fkh2 in efficient septum cleavage [12].

Analytical, diagnostic and therapeutic context of FKH2

  • 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 [8].


  1. Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth. Zhu, G., Spellman, P.T., Volpe, T., Brown, P.O., Botstein, D., Davis, T.N., Futcher, B. Nature (2000) [Pubmed]
  2. Forkhead-like transcription factors recruit Ndd1 to the chromatin of G2/M-specific promoters. Koranda, M., Schleiffer, A., Endler, L., Ammerer, G. Nature (2000) [Pubmed]
  3. Recruitment of Thr 319-phosphorylated Ndd1p to the FHA domain of Fkh2p requires Clb kinase activity: a mechanism for CLB cluster gene activation. Reynolds, D., Shi, B.J., McLean, C., Katsis, F., Kemp, B., Dalton, S. Genes Dev. (2003) [Pubmed]
  4. Forkhead genes in transcriptional silencing, cell morphology and the cell cycle. Overlapping and distinct functions for FKH1 and FKH2 in Saccharomyces cerevisiae. Hollenhorst, P.C., Bose, M.E., Mielke, M.R., Müller, U., Fox, C.A. Genetics (2000) [Pubmed]
  5. A forkhead transcription factor is important for true hyphal as well as yeast morphogenesis in Candida albicans. Bensen, E.S., Filler, S.G., Berman, J. Eukaryotic Cell (2002) [Pubmed]
  6. Forkhead transcription factors, Fkh1p and Fkh2p, collaborate with Mcm1p to control transcription required for M-phase. Kumar, R., Reynolds, D.M., Shevchenko, A., Shevchenko, A., Goldstone, S.D., Dalton, S. Curr. Biol. (2000) [Pubmed]
  7. Saccharomyces forkhead protein Fkh1 regulates donor preference during mating-type switching through the recombination enhancer. Sun, K., Coïc, E., Zhou, Z., Durrens, P., Haber, J.E. Genes Dev. (2002) [Pubmed]
  8. The forkhead protein Fkh2 is a component of the yeast cell cycle transcription factor SFF. Pic, A., Lim, F.L., Ross, S.J., Veal, E.A., Johnson, A.L., Sultan, M.R., West, A.G., Johnston, L.H., Sharrocks, A.D., Morgan, B.A. EMBO J. (2000) [Pubmed]
  9. Regulation of cell cycle-specific gene expression through cyclin-dependent kinase-mediated phosphorylation of the forkhead transcription factor Fkh2p. Pic-Taylor, A., Darieva, Z., Morgan, B.A., Sharrocks, A.D. Mol. Cell. Biol. (2004) [Pubmed]
  10. Cell cycle-dependent transcription in yeast: promoters, transcription factors, and transcriptomes. Wittenberg, C., Reed, S.I. Oncogene (2005) [Pubmed]
  11. Cell cycle-regulated transcription through the FHA domain of Fkh2p and the coactivator Ndd1p. Darieva, Z., Pic-Taylor, A., Boros, J., Spanos, A., Geymonat, M., Reece, R.J., Sedgwick, S.G., Sharrocks, A.D., Morgan, B.A. Curr. Biol. (2003) [Pubmed]
  12. Characterisation of two novel fork-head gene homologues of Schizosaccharomyces pombe: their involvement in cell cycle and sexual differentiation. Szilagyi, Z., Batta, G., Enczi, K., Sipiczki, M. Gene (2005) [Pubmed]
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