Disease relevance of MUC1

• The upstream region of STA2 was amplified by the polymerase chain reaction (PCR) and fused to the Escherichia coli lacZ gene [1].
• For the secretion of Bacillus stearothermophilus alpha-amylase from yeast, a recombinant plasmid pGAT17 was constructed by fusing B. stearothermophilus alpha-amylase structural gene in frame to the promoter and signal sequence of Saccharomyces diastaticus glucoamylase I gene (STA1) [2].

High impact information on MUC1

• The epigenetic state of FLO11 is heritable for many generations and regulated by the histone deacetylase (HDAC) Hda1p [3].
• Epigenetic silencing of FLO11 regulates a key developmental switch: when FLO11 is expressed, diploid cells form pseudohyphal filaments; when FLO11 is silent, the cells grow in yeast form [3].
• Moreover, ploidy regulation of the FLO11 gene had direct consequences for yeast development [4].
• Saccharomyces cells secrete aromatic alcohols that stimulate morphogenesis by inducing the expression of FLO11 through a Tpk2p-dependent mechanism [5].
• Thus, like the promoters of the key developmental genes, HO and IME1, the FLO11 promoter is large and complex, endowing it with the ability to integrate multiple inputs [6].

Biological context of MUC1

• Repression of FLO11-dependent flocculation in diploids is conferred by the mating-type repressor al/alpha2 [7].
• The sequence of FLO11 reveals a 4,104-bp open reading frame on chromosome IX whose predicted product is similar in overall structure to the class of yeast serine/threonine-rich GPI-anchored cell wall proteins [7].
• When a green fluorescent protein fusion of FLO11 was expressed from the FLO11 promoter on a single-copy plasmid, fluorescence was observed in vivo at the periphery of cells [7].
• FLO11 differs from all other yeast flocculins in that it is located near a centromere rather than a telomere, and its expression is regulated by mating type [7].
• The FLO11-encoded flocculin is required for a variety of important phenotypes in Saccharomyces cerevisiae, including flocculation, adhesion to agar and plastic, invasive growth, pseudohyphae formation and biofilm development [8].

Anatomical context of MUC1

• The oxidation of NADH in submitochondrial particles isolated from MUC1, MUC2 and MUC3 mucidin-resistant mutants of Saccharomyces cerevisiae is specifically resistant to mucidin [9].
• Immunization with tumour antigen MUC1 conjugated to oxidized mannan (OM) or reduced mannan (RM) induced differential immune responses in mice, and only mice immunized with OM-MUC1 elicited strong MUC1-specific cytotoxic T lymphocyte responses and protected mice from a MUC1 tumour challenge [10].
• The sta2 gene, conferring the ability to metabolize starch was transferred from an auxotrophic haploid strain of S. cerevisiae (S. diastaticus) and the melibiose-metabolism (mel) gene(s), from S. kluyveri, to the kar1-1 mutant [K5-5A; (alpha ade2 his4 can1 gal) by normal mating and protoplast fusion [11].

Associations of MUC1 with chemical compounds

• We show here that Snf1 regulates transcription of FLO11, which encodes a cell surface glycoprotein required for invasive growth [12].
• We report that Flo11p-dependent flocculation is inhibited by mannose, but not by glucose, maltose or sucrose [8].
• In MUC1 and MUC2 mutants, the red shift is not induced by mucidin, while that promoted by antimycin A and 2-n-heptyl-4-hydroxyquinoline N-oxide are normal [9].
• These morphogenetic events are induced by starvation for glucose or nitrogen and require the cell surface protein Flo11p [13].
• A conditional vhs3 tetO:HAL3 double mutant displays, in the presence of doxycycline, a flocculation phenotype that is dependent on the presence of Flo8 and Flo11 [14].

Physical interactions of MUC1

• The absence of the Isw2p-Itc1p chromatin-remodelling complex induces mating type-specific and Flo11p-independent invasive growth of Saccharomyces cerevisiae [15].
• Flo8 and Mss11 bind cooperatively to the inverted repeat sequence TTTGC-n-GCAAA (n = 97) in UAS1-2 of the STA1 promoter [16].
• The NRG1 gene encodes a 25-kDa C2H2 zinc finger protein which specifically binds to two regions in the upstream activation sequence of the STA1 gene, as judged by gel retardation and DNase I footprinting analyses [17].

Regulatory relationships of MUC1

• Recruitment of the Swi/Snf complex by Ste12-Tec1 promotes Flo8-Mss11-mediated activation of STA1 expression [16].
• In the final step, Flo8 and Mss11 directly promote association of RNA polymerase II with the STA1 promoter to activate STA1 expression [16].
• In haploid cells, Cdc42p is able to regulate invasive growth dependent on and independent of FLO11 gene expression [18].
• GPR1 regulates filamentous growth through FLO11 in yeast Saccharomyces cerevisiae [19].
• In addition, Gcn4p controls expression of FLO11 by affecting two basal upstream activation sequences (UASB) [13].

Other interactions of MUC1

• We show that MUC1 mediates the effect of Msn1p and Mss11p on invasive growth [20].
• FLO11 transcription, which correlates with the level of invasive growth, is low in cln1 cln2 mutants and high in grr1 cells (defective in proteolysis of Cln1,2), suggesting that Cln1,2/Cdks regulate the pseudohyphal transcriptional program [21].
• KEM1 affected the level of FLO11 transcripts and the expression of the filamentation-associated reporter genes, Ty1-lacZ and FLO11-lacZ [22].
• Mutational analysis of TEC1 revealed that TCS control, FLO11 expression, and haploid invasive growth require the C terminus of Tec1p [23].
• Genetic evidence indicates that Tpk2 acts upstream of Sfl1 in the regulation of Flo11 [24].

Analytical, diagnostic and therapeutic context of MUC1

• Northern blot analysis revealed that the transcriptional level of FLO11, which encodes a recently identified cell surface flocculin required for pseudohyphal growth, was reduced in Deltagpr1 mutant strain [19].
• Allelism tests indicated that the mucidin resistance mutations fell into two genetic loci (MUC1 and MUC2) which were apparently not closely linked in the mitochondrial genome [25].
• Chromosomes were separated by pulsed field gel electrophoresis and blots were probed with radiolabelled STA2 and marker DNA from specific yeast chromosomes [26].
• Molecular cloning and characterization of the STA2 glucoamylase gene of Saccharomyces diastaticus [27].
• The enzyme encoded by the STA2 gene (glucoamylase II) has been purified from culture medium to near homogeneity by ethanol precipitation, Trisacryl M DEAE chromatography, and HPLC gel filtration [28].

References