High impact information on BEM2

• BEM2 of Saccharomyces cerevisiae encodes a Rho-type GTPase-activating protein that is required for proper bud site selection at 26 degrees C and for bud emergence at elevated temperatures [1].
• We show here that the temperature-sensitive growth phenotype of bem2 mutant cells can be suppressed by increased dosage of the GIC1 gene [1].
• Bem2p is a Rho-GTPase activating protein (GAP) previously shown to act on Rho1p, and we now show that it also acts on Cdc42p, the GTPase primarily responsible for establishment of cell polarity in yeast [2].
• Whereas the morphogenesis role of Bem2p required GAP activity, the checkpoint role of Bem2p did not [2].
• The bud emergence mutants bem1 and bem2 and mutants defective in the septins do not affect Spa2p localization to the bud tip [3].

Biological context of BEM2

• Cells lacking both BEM2 and SIT4 exhibit a synthetic lethal phenotype even in the presence of the SSD1-v1 suppressor [4].
• These genetic interactions together suggest that protein phosphorylation and dephosphorylation play an important role in the BEM2-mediated process of polarized cell growth [4].
• These results indicate that this synthetic lethality approach provides a sensitive screen for the isolation of mutations affecting morphogenesis, many of which are likely to be in nonessential genes, like BEM2 and SLT2 [5].
• The most frequently identified gene that arose from the bem1 synthetic-lethal screen was the bud-emergence gene BEM2 (Bender and Pringle. 1991. Mol. Cell Biol. 11:1295-1395), which is allelic with IPL2 (increase in ploidy; Chan and Botstein, 1993. Genetics. 135:677-691) [6].
• Point mutations that alter single conserved cysteine residues within either LIM domain result in mutant forms of Dbm1p that can no longer function in bud site selection but instead are capable of rescuing the inviability of bem2 mutants at 35 degrees C [7].

Anatomical context of BEM2

• These data therefore provide a genetic link between the GAP encoded by BEM2 and the functional organization of microfilaments [8].
• In addition, we show that bem2 mutations confer benomyl sensitivity and have abnormal microtubule arrays, suggesting that the BEM2 product may also be involved directly or indirectly in regulating microtubule function [8].
• It is concluded that the function of the BEM2 gene product is essential for the maintenance of a functional cell wall [9].
• Mutants in the BEM2 gene have been reported to display loss of cell polarity and depolarization of the actin cytoskeleton, causing a bud-emergence defect [9].

Other interactions of BEM2

• Interactions between the bud emergence proteins Bem1p and Bem2p and Rho-type GTPases in yeast [6].
• CDC55 encodes the putative regulatory B subunit of protein phosphatase 2A, and mutations in BEM2 have previously been identified as suppressors of the cdc55-1 mutation [4].
• Previous studies have shown that BEM2, which encodes a GTPase-activating protein (GAP) that is specific for the Rho-type GTPase Rho1p in vitro, is required for proper bud site selection and bud emergence [7].
• We also report the identification of a new gene, BEM3, that is a multicopy suppressor of the temperature-sensitive lethality caused by mutations in the bud emergence gene BEM2 [10].
• Among eight potential yeast RhoGAPs, Lrg1p is the only member that negatively regulates GS activity: mutations in the rest of GAPs, including bem2, Deltabem3, Deltasac7, Deltabag7, Deltarga1, Deltarga2 and Deltargd1, do not suppress impairment of 1,3-beta-glucan synthesis [11].

Analytical, diagnostic and therapeutic context of BEM2

• Molecular cloning and genetic mapping show that IPL1 is a newly identified gene, whereas IPL2 is allelic to BEM2, which is required for normal bud growth [12].

References