SUMMARY PARAGRAPH for MBP1
Mbp1p is a DNA-binding protein that forms MBF complex (Mlu1 cell cycle box [MCB] Binding Factor) with Swi6p. MBF is a sequence-specific transcription factor that regulates gene expression during the G1/S transition of the cell cycle (1, 2, 3, and 4). Several genes activated or repressed by MBF have been identified, many of which are involved in DNA synthesis and DNA repair (for example, CDC21, CDC8, and CDC9, and also G1 cyclins) (1, 5, 6, 3, and 7). Mbp1p can bind DNA directly without Swi6p. Swi6p does not bind DNA but acts as a trans-activator for MBF function (1, 8, 9). DNA footprinting studies suggest that MBF binds to DNA as a single Mbp1p/Swi6p heterodimer in an orientation-independent manner (10), with the most-often reported MCB consensus sequence bound by MBF being 5'-ACGCGT-3' (5, 11, 12, 6). See also 6, 13, 12, and 14 for variations.
Mbp1p is topologically related to winged helix-turn-helix transcription factors including Swi4p and Swi6p in S. cerevisiae; cdc10, res1, and res2 in S. pombe; and human hepatic nuclear factor 3-gamma (HNF3gamma) (10, 15). The N-terminal 112 amino acids are 50% identical to Swi4p and are sufficient to bind DNA, and the C-terminal residues 735-813 are 44% identical to Swi4p and can bind Swi6p (1, 10). The central portion of Mbp1p contains 2 ankyrin repeats separated by a short spacer region, a structure similar to that found in Swi4p (1).
mbp1 null mutants show deregulated expression of DNA synthesis genes and populations of vegetatively growing cells show a slight increase in average cell volume and budding index (7). The viability of mbp1 mutants suggests the existence of additional mechanisms for regulation of MBF target genes (1, 7). Indeed, Swi6p forms the similar SBF complex (Swi4/6 cell cycle box [SCB] Binding Factor) with Swi4p. Strains deleted for both MBP1 and SWI4 are inviable, demonstrating that SBF affects MBF-mediated transcription (1, 7). Probably owing to the extensive similarity between Mbp1p and Swi4p, these proteins show modest discrimination between their cognate binding sites in vivo (9, 13), displaying a 4-6-fold preference for their own site over that of the other transcription factor (10). However, each protein shows greater than 100-fold preference for the other's consensus sequence over non-specific sequences (10). A number of genome-wide analyses have uncovered over 100 putative targets for both MBF and SBF (13, 11, 12, 14).
Despite this apparent specificity, the presence of MCB or SCB motifs alone is not predictive of whether MBF, SBF, or both will bind to or regulate a promoter, suggesting a great complexity in the transcriptional regulation mediated through these binding sites (7). Indeed, there is physical and genetic evidence that Mbp1p interacts with Skn7p and this complex is distinct from MBF and functions in transcription regulation (16). In meiosis, MCBs can be regulated independently of Mbp1p (17).
Last updated: 2006-05-15