Dual Regulation by Pairs of Cyclin-Dependent Protein Kinases and Histone Deacetylases Controls G1 Transcription in Budding Yeast

Abstract

Initiation of the cell division cycle in yeast is controlled by two distinct kinases that coordinately regulate the interaction of Whi5, a repressor of initiation, with histone deacetylases.

The Importance of Conserved Features of Yeast Actin-Binding Protein 1 (Abp1p): The Conditional Nature of Essentiality

“…We have demonstrated that Abp1p is phosphorylated at Thr526 by the Cdc28p and Pho85p kinases (Figure 4), which recognize the same consensus phosphorylation sites and are functionally interchangeable under some conditions (Nishizawa et al 1998;Ptacek et al 2005;Huang et al 2007Huang et al , 2009Sopko et al 2007;Enserink and Kolodner 2010). While other sites of Cdc28p-mediated phosphorylation have been detected in Abp1p through large-scale phosphoproteomic studies (Ficarro et al 2002;Ubersax et al 2003;Holt et al 2009), Thr526 is the first phosphorylation site within Abp1p to be experimentally verified through mutagenesis.…”

Hog1 Targets Whi5 and Msa1 Transcription Factors To Downregulate Cyclin Expression upon Stress

“…Whi5 is strongly bound to SBF-dependent promoters, which keeps transcription blocked. However, Cdc28 (the main cyclin-dependent kinase [CDK] in yeast) and Pho85, in association with the G 1 cyclin Cln3 and Pcl9, respectively, can phosphorylate Whi5, causing its eviction from these promoters (14)(15)(16), thereby allowing its active export from the nucleus by the karyopherin Msn5 (17,18). These effects on Whi5 enable RNA polymerase (Pol) II to trigger SBF-dependent transcription, generating an initial burst of Cln2.…”

Cell Cycle Regulation of DNA Replication in S. cerevisiae

“…Whi5 is a transcriptional suppressor that interacts with SBF, a transcription factor complex required for transcription of genes involved in cell cycle entry and DNA replication (the socalled G1 transcriptional program). Whi5 also recruits histone deacetylases (HDACs) that maintain the chromatin surrounding the SBF-Whi5 complex in a repressive state (Huang, Kaluarachchi et al 2009;Wang, Carey et al 2009). Thus, as long as Whi5 is bound to SBF, the cell cannot enter the cell cycle.…”

“…Thus, as long as Whi5 is bound to SBF, the cell cannot enter the cell cycle. However, phosphorylation of Whi5 by Cln3-Cdk1 induces the release of Whi5 and HDACs from SBF (Costanzo, Nishikawa et al 2004;de Bruin, McDonald et al 2004;Huang, Kaluarachchi et al 2009;Wang, Carey et al 2009). SBF then activates transcription of the G1 transcriptional program.…”