Phosphorylation of Cdc5 regulates its accumulation

• Main Authors: Simpson-Lavy Kobi J, Brandeis Michael
• Format: Article
• Language: English
• Published: BMC 2011-12-01
• Series: Cell Division
• Subjects: Cdk1; Cdc28; Clb2; Swe1; Polo; mitosis; phosphorylation; APC/C; Cdh1
• Online Access: http://www.celldiv.com/content/6/1/23

<p>Abstract</p> <p>Background</p> <p>Cdc5 (polo kinase/Plk1) is a highly conserved key regulator of the <it>S. cerevisiae </it>cell cycle from S-phase until cytokinesis. However, much of the regulatory mechanisms that govern Cdc5 remain to be determined. Cdc5 is phosphorylated on up to 10 sites during mitosis. In this study, we investigated the function of phosphorylation site T23, the only full consensus Cdk1 (Cdc28) phosphorylation site present.</p> <p>Findings</p> <p><it>Cdc5^T23A</it>introduces a degron that reduces its cellular amount to undetectable levels, which are nevertheless sufficient for normal cell proliferation. The degron acts <it>in cis </it>and is reversed by N-terminal GFP-tagging. Cdk1 kinase activity is required to maintain Cdc5 levels during G2. This, Cdk1 inhibited, Cdc5 degradation is APC/C^Cdh1independent and requires new protein synthesis. Cdc5^T23Eis hyperactive, and reduces the levels of Cdc5 (<it>in trans</it>) and drastically reduces Clb2 levels.</p> <p>Conclusions</p> <p>Phosphorylation of Cdc5 by Cdk1 is required to maintain Cdc5 levels during G2. However, phosphorylation of T23 (probably by Cdk1) caps Cdc5 and other <it>CLB2 </it>cluster protein accumulation, preventing potential protein toxicity, which may arise from their overexpression or from APC/C^Cdh1inactivation.</p>