Disease relevance of MBP1

• A 124-residue N-terminal fragment corresponding to the DNA-binding domain of the Saccharomyces cerevisae cell-cycle transcription factor MBP-1 has been expressed with a hexahistidine affinity tag in E. coli and purified to apparent homogeneity [1].

High impact information on MBP1

• The related Swi4 and Mbp1 proteins are the DNA-binding components of the respective factors, and Swi6 mayhave a regulatory function [2].
• Strains deleted for both MBP1 and SWI4 were inviable, demonstrating that transcriptional activation by MBF and SBF has an important role in the transition from G1 to S phase [3].
• In contrast, other known Start regulators Mbp1 and Cln3 are not needed for coherence but ensure regular timing of Start onset [4].
• When fused to the LexA DNA-binding domain, Xbp1 acts as transcriptional repressor, defining it as the first repressor in the Swi4/Mbp1 family and the first potential negative regulator of transcription induced by stress [5].
• Similarly, high overexpression of Mbp1 is lethal and can be suppressed by skn7 mutations [6].

Biological context of MBP1

• We further demonstrate that during meiosis MCBs function as effective transcriptional activators independent of MBP1 [7].
• Association of the cell cycle transcription factor Mbp1 with the Skn7 response regulator in budding yeast [6].
• Pct1+ is related to, but distinct from, the res1+/sct1+ gene that also encodes a p85cdc10 partner. p73pct1 has centrally located ankyrin repeats and a putative amino-terminal DNA-binding domain that has extensive sequence similarity to the DNA-binding domains of the Saccharomyces cerevisiae SWI4 and MBP1 proteins [8].
• In proliferating S. cerevisiae, genes whose products function in DNA replication are regulated by the MBF transcription factor composed of Mbp1 and Swi6 that binds to consensus MCB sequences in target promoters [7].
• Changes in the backbone amide proton and nitrogen chemical shifts upon DNA binding have enabled us to experimentally define a DNA-binding surface on the core N-terminal domain of Mbp1 that is associated with a putative winged helix-turn-helix motif [9].

Anatomical context of MBP1

• The HeLa cDNA sequence is highly similar to MBP1 and it encodes peptides obtained directly from human erythrocyte S5a [10].
• Based upon the MBP1 cDNA sequence we have now isolated a HeLa cell cDNA coding for human S5a [10].
• CONCLUSIONS: Despite little sequence similarity, the structure within the core region of the Mbp1 N-terminal domain exhibits a similar fold to that of the DNA-binding domains of other proteins, such as hepatocyte nuclear factor-3gamma and histone H5 from eukaryotes, and the prokaryotic catabolite gene activator [11].

Associations of MBP1 with chemical compounds

• The response to glucose is partially suppressed by inactivation of SWI4, but not MBP1, which is consistent with the dependence of MCB core elements upon the SCB-binding transcription factor (SBF) [12].
• However, alanine substitution of two lysine residues (116 and 122) within the C-terminal extension (tail) of Mbp1 considerably reduces the apparent affinity for an MCB (MluI cell-cycle box) containing oligonucleotide [9].

Other interactions of MBP1

• Furthermore, elevated MBP1, a transcriptional regulator of cyclins, altered the transcriptional start site in CLN3 mRNA, shifting it 45 nucleotides upstream of the normal [13].
• Surprisingly, deletion of MBP1 had no effect on the meiotic expression of CLB5, which is purportedly controlled by MBF [7].
• MBF is composed of Mbp1 and Swi6 and activates the transcription of genes required for DNA synthesis [14].
• On the contrary, loss of MSN5 has no effect on the closely related transcription factor MBF (composed of the Mbp1p and Swi6p proteins) [15].
• For most G1/S-regulated genes that we tested in a cdc20 block-release protocol for cell-cycle synchronization, removal of both Swi4 and Mbp1 was necessary and sufficient to essentially eliminate cell-cycle-regulated expression [16].

Analytical, diagnostic and therapeutic context of MBP1

• However, a physical interaction between Skn7 and Mbp1 was detected using two-hybrid assays and GST pulldowns [6].
• Expression, purification, and crystallization of the DNA-binding domain from the Saccharomyces cerevisae cell-cycle transcription factor MBP-1 [1].

References