Title

Regulation of a transcription factor network by Cdk1 coordinates late cell cycle gene expression

UMMS Affiliation

Program in Gene Function and Expression; Program in Molecular Medicine

Date

5-2-2014

Document Type

Article

Disciplines

Biochemistry | Cellular and Molecular Physiology | Genetics | Genetics and Genomics

Abstract

To maintain genome stability, regulators of chromosome segregation must be expressed in coordination with mitotic events. Expression of these late cell cycle genes is regulated by cyclin-dependent kinase (Cdk1), which phosphorylates a network of conserved transcription factors (TFs). However, the effects of Cdk1 phosphorylation on many key TFs are not known. We find that elimination of Cdk1-mediated phosphorylation of four S-phase TFs decreases expression of many late cell cycle genes, delays mitotic progression, and reduces fitness in budding yeast. Blocking phosphorylation impairs degradation of all four TFs. Consequently, phosphorylation-deficient mutants of the repressors Yox1 and Yhp1 exhibit increased promoter occupancy and decreased expression of their target genes. Interestingly, although phosphorylation of the transcriptional activator Hcm1 on its N-terminus promotes its degradation, phosphorylation on its C-terminus is required for its activity, indicating that Cdk1 both activates and inhibits a single TF. We conclude that Cdk1 promotes gene expression by both activating transcriptional activators and inactivating transcriptional repressors. Furthermore, our data suggest that coordinated regulation of the TF network by Cdk1 is necessary for faithful cell division.

Comments

Citation: Landry BD, Mapa CE, Arsenault HE, Poti KE, Benanti JA. Regulation of a transcription factor network by Cdk1 coordinates late cell cycle gene expression. EMBO J. 2014 May 2;33(9):1044-60. doi: 10.1002/embj.201386877. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Keywords

Cdk1, Cell Cycle, Mitosis Proteolysis, Transcription