The CK2 phosphorylation of catalytic domain of Cdc34 modulates its activity at the G₁to S transition inSaccharomyces cerevisiae

Abstract

, we show, by direct mass spectrometry analysis, that Cdc34 is phosphorylated in vitro and in vivo by CK2 on Ser130 and Ser167, and that the phosphoserines 130 and 167 are not present after CK2 inactivation in a cka1Δcka2-8 ts strain. CK2 phosphorylation of Ser130 and Ser167 strongly stimulates Cdc34 ubiquitin charging in vitro. The Cdc34 S130AS167A mutant shows a basal ubiquitin charging activity which is indistinguishable from that of wild type but is not activated by CK2 phosphorylation and its expression fails to complement a cdc34-2 ts yeast strain, supporting a model in which activation of Cdc34 involves CK2-mediated phosphorylation of its catalytic domain.

New Insight Into the Role of the Cdc34 Ubiquitin-Conjugating Enzyme in Cell Cycle Regulation via Ace2 and Sic1

“…CKA2, one of two catalytic subunits of Casein Kinase II, phosphorylates any of six serines within the acidic C terminus of Cdc34, and it is synthetically lethal with CDC34 tm ( Figure 5B). Phosphorylation of Cdc34 by Casein Kinase 2 increases its activity against Sic1 (Sadowski et al 2007;Coccetti et al 2008). Furthermore, Casein Kinase 2 also phosphorylates Ser201 of Sic1, which promotes Sic1 degradation (Coccetti et al 2006;Tripodi et al 2007).…”

Time schedule-dependent effect of the CK2 inhibitor TBB on PC-3 human prostate cancer cell viability

“…CK2 has been shown to be necessary for progression of cells through the cell cycle (2-4) because of phosphorylation of several cell cycle regulators and mitotic proteins (5)(6)(7). It has also been identified as a suppressor of apoptosis (8)(9)(10)(11).…”

Multimodal Mechanism of Action for the Cdc34 Acidic Loop

“…In 2007, Pan and colleagues (26) were the first to show that the mutation of acidic residues in the human Cdc34 acidic loop also leads to a loss of Cdc34 activity in vitro. More recently, molecular dynamics simulations predicted changes in the conformations of the yeast Cdc34 acidic loop in response to the phosphorylation of two active site serine residues previously identified as potential sites of casein kinase 2 phosphorylation (27,28). Finally, members of the ubiquitin-conjugating enzyme family Ube2G2 (called Ubc7 in yeast) also contain an acidic loop with four conserved acidic residues, and their mutation also leads to the loss of human Ube2G2 activity in vitro (29).…”