Cell cycle-regulated transcription through the FHA domain of Fkh2p and the coactivator Ndd1p.
Curr Biol
; 13(19): 1740-5, 2003 Sep 30.
Article
in En
| MEDLINE
| ID: mdl-14521842
ABSTRACT
Recent studies in Saccharomyces cerevisiae by using global approaches have significantly enhanced our knowledge of the components involved in the transcriptional regulation of the cell cycle. The Mcm1p-Fkh2p complex, in combination with the coactivator Ndd1p, plays an important role in the cell cycle-dependent expression of the CLB2 gene cluster during the G2 and M phases ([4-7]; see [8-10]for reviews). Fkh2p is phosphorylated in a cell cycle-dependent manner, and peak phosphorylation occurs coincidentally with maximal expression of Mcm1p-Fkh2p-dependent gene expression. However, the mechanism by which this complex is activated in a cell cycle-dependent manner is unknown. Here, we demonstrate that the forkhead-associated (FHA) domain of Fkh2p directs cell cycle-regulated transcription and that the activity of this domain is dependent on the coactivator Ndd1p. 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. Furthermore, mutation of the FHA domain blocks these phosphorylation-dependent interactions and abolishes transcriptional activity. Our data therefore link the transcriptional activity of the FHA domain with cell cycle-dependent phosphorylation of the coactivator Ndd1p and reveal a mechanism that permits precise temporal activation of the Mcm1p-Fkh2p complex.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Transcription, Genetic
/
Cell Cycle
/
Cell Cycle Proteins
/
Cyclin B
/
Saccharomyces cerevisiae Proteins
Type of study:
Prognostic_studies
Language:
En
Journal:
Curr Biol
Journal subject:
BIOLOGIA
Year:
2003
Document type:
Article
Affiliation country:
United kingdom