The emerging regulatory potential of SCF-mediated polyubiquitination and proteolysis of the Met4 transcriptional activator-0

Assembly between Met4 and cofactors (A), and that the dissociation of Met4 homodimers by SCF(B, ) is necessary to stabilize and/or rearrange the protein-protein interactions within the Met4/Met28/Cbf1 complex, triggering its proper assembly (B). The low abundance of SCFsuggests that proteolysis of the remaining Met4 molecule occupying SCF(B, ) is necessary for SCFrecycling (B, ). As a result, 'two stepping' with SCFcould be necessary for each round of Met4 activity at a promoter (all steps involving SCFare marked in blue). The stabilizing effect of cofactors on the SCF-Met4 interaction ('tight complex', note exposure of the UIM domain in Met4) allows Met4 inhibition by polyubiquitination only (C), unless methionine (D) or cysteine (D) is available to destabilize the tight interaction between Met4 and SCF, allowing Met4 proteolysis. Disassembly of the Met4 complex by the proteasome could link activation of methionine biosynthesis to cell division by releasing the DNA binding cofactors Cbf1 and Met31/32 from promoters (D), which, at least in the case of Cbf1, would make it available for its cell division role. Dissociation of Met4 prior to its proteolysis could protect the cofactors and SCFfrom effects of the proteasome-mediated disassembly (D), preventing Cbf1 and/or Met31/32 release. See text for details.<p><b>Copyright information:</b></p><p>Taken from "The emerging regulatory potential of SCF-mediated polyubiquitination and proteolysis of the Met4 transcriptional activator"</p><p>http://www.celldiv.com/content/3/1/11</p><p>Cell Division 2008;3():11-11.</p><p>Published online 25 Jul 2008</p><p>PMCID:PMC2526995.</p><p></p