生物谷報道：有關(guān)G1/S調(diào)控的機(jī)理，新發(fā)現(xiàn)一個新蛋白Whi5,，是G1周期的抑制子,。最新一期Cell上有兩篇文章報道了這一發(fā)現(xiàn)，同時是封面文章,，并作了評論,。

   Cyclin-dependent kinase (CDK) activity initiates the eukaryotic cell division cycle by turning on a suite of gene expression in late G1 phase. In metazoans, CDK-dependent phosphorylation of the retinoblastoma tumor suppressor protein (Rb) alleviates repression of E2F and thereby activates G1/S transcription. However, in yeast, an analogous G1 phase target of CDK activity has remained elusive. Here we show that the cell size regulator Whi5 inhibits G1/S transcription and that this 

inhibition is relieved by CDK-mediated phosphorylation. Deletion of WHI5 bypasses the requirement for upstream activators of the G1/S transcription factors SBF/MBF and thereby accelerates the G1/S transition. Whi5 is recruited to G1/S promoter elements via its interaction with SBF/MBF in vivo and in vitro. In late G1 phase, CDK-dependent phosphorylation dissociates Whi5 from SBF and drives Whi5 out of the nucleus. Elimination of CDK activity at the end of mitosis allows Whi5 to reenter the nucleus to again repress G1/S transcription. These findings harmonize G1/S control in eukaryotes.

第二篇

G1-specific transcriptional activation by Cln3/CDK initiates the budding yeast cell cycle. To identify targets of Cln3/CDK, we analyzed the SBF and MBF transcription factor complexes by multidimensional protein interaction technology (MudPIT). Whi5 was identified as a stably bound component of SBF but not MBF. Inactivation of Whi5 leads to premature expression of G1-specific genes and budding, whereas overexpression retards those processes. Whi5 inactivation bypasses the requirement for Cln3 both for transcriptional activation and cell cycle initiation. Whi5 associates with G1-specific promoters via SBF during early G1 phase, then dissociates coincident with transcriptional activation. Dissociation of Whi5 is promoted by Cln3 in vivo. Cln/CDK phosphorylation of Whi5 in vitro promotes its dissociation from SBF complexes. Mutation of putative CDK phosphorylation sites, at least five of which are phosphorylated in vivo, strongly reduces SBF-dependent transcription and delays cell cycle initiation. Like mammalian Rb, Whi5 is a G1-specific transcriptional repressor antagonized by CDK.

原文：

CDK Activity Antagonizes Whi5, an Inhibitor of G1/S Transcription in Yeast
Michael Costanzo, Joy L. Nishikawa, Xiaojing Tang, Jonathan S. Millman, Oliver Schub, Kevin Breitkreuz, Danielle Dewar, Ivan Rupes, Brenda Andrews, and Mike Tyers
[Summary] [Full Text] [PDF] [Supplemental Data]

Cln3 Activates G1-Specific Transcription via Phosphorylation of the SBF Bound Repressor Whi5
Robertus A.M. de Bruin, W. Hayes McDonald, Tatyana I. Kalashnikova, John Yates, and Curt Wittenberg
[Summary] [Full Text] [PDF] [Supplemental Data]