Recruitment of Thr 319-phosphorylated Ndd1p to the FHA domain of Fkh2p requires Clb kinase activity: a mechanism for CLB cluster gene activation.

Abstract:

: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. We show that the activation of this mitotic transcriptional program is dependent on the recruitment of Ndd1p, a coactivator that performs its essential function by acting through Fkh2p. Although an essential gene, NDD1 is dispensable in cells expressing a truncated form of Fkh2p lacking its C terminus. When phosphorylated on T319, Ndd1p is recruited to CLB cluster promoters by association with the forkhead-associated (FHA) domain of Fkh2p. Substitution of T319 for alanine significantly reduces recruitment of Ndd1p, resulting in loss of normal transcriptional regulation, severe impairment of cell growth, and a budding defect reminiscent of cells with a Cdk-Clb kinase deficiency. Finally, we show that phosphorylation of T319 and recruitment of Ndd1p to CLB2 and SWI5 promoters is dependent on Cdc28-Clb kinase activity. These data provide a model describing the activation of G2/M transcription through the phosphorylation of Ndd1p by Cdc28-Clb kinase activity.

journal_name

Genes Dev

journal_title

Genes & development

authors

Reynolds D,Shi BJ,McLean C,Katsis F,Kemp B,Dalton S

doi

10.1101/gad.1074103

subject

Has Abstract

pub_date

2003-07-15 00:00:00

pages

1789-802

issue

14

eissn

0890-9369

issn

1549-5477

pii

17/14/1789

journal_volume

17

pub_type

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