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Factor Downstream (factor + downstream)
Selected AbstractsRole of the Slt2 mitogen-activated protein kinase pathway in cell wall integrity and virulence in Candida glabrataFEMS YEAST RESEARCH, Issue 3 2010Taiga Miyazaki Abstract The Slt2 mitogen-activated protein kinase pathway plays a major role in maintaining fungal cell wall integrity. In this study, we investigated the effects of SLT2 deletion and overexpression on drug susceptibility and virulence in the opportunistic fungal pathogen Candida glabrata. While the ,slt2 strain showed decreased tolerance to elevated temperature and cell wall-damaging agents, the SLT2 -overexpressing strain exhibited increased tolerance to these stresses. A mutant lacking Rlm1, a transcription factor downstream of Slt2, displayed a cell wall-associated phenotype intermediate to that of the ,slt2 strain. When RLM1 was overexpressed, micafungin tolerance was increased in the wild-type strain and partial restoration of the drug tolerance was observed in the ,slt2 background. It was also demonstrated that echinocandin-class antifungals were more effective against C. glabrata under acidic conditions or when used concurrently with the chitin synthesis inhibitor nikkomycin Z. Finally, in a mouse model of disseminated candidiasis, the deletion and overexpression of C. glabrata SLT2 resulted in mild decreases and increases, respectively, in the CFUs from murine organs compared with the wild-type strain. These fundamental data will help in further understanding the mechanisms of cell wall stress response in C. glabrata and developing more effective treatments using echinocandin antifungals in clinical settings. [source] Caenorhabditis elegans PI3K mutants reveal novel genes underlying exceptional stress resistance and lifespanAGING CELL, Issue 6 2009Srinivas Ayyadevara Summary Two age-1 nonsense mutants, truncating the class-I phosphatidylinositol 3-kinase catalytic subunit (PI3KCS) before its kinase domain, confer extraordinary longevity and stress-resistance to Caenorhabditis elegans. These traits, unique to second-generation homozygotes, are blunted at the first generation and are largely reversed by additional mutations to DAF-16/FOXO, a transcription factor downstream of AGE-1 in insulin-like signaling. The strong age-1 alleles (mg44, m333) were compared with the weaker hx546 allele on expression microarrays, testing four independent cohorts of each allele. Among 276 genes with significantly differential expression, 92% showed fewer transcripts in adults carrying strong age-1 alleles rather than hx546. This proportion is significantly greater than the slight bias observed when contrasting age-1 alleles to wild-type worms. Thus, transcriptional changes peculiar to nonsense alleles primarily involve either gene silencing or failure of transcriptional activation. A subset of genes responding preferentially to age-1- nonsense alleles was reassessed by real-time polymerase chain reaction, in worms bearing strong or weak age-1 alleles; nearly all of these were significantly more responsive to the age-1(mg44) allele than to age-1(hx546). Additional mutation of daf-16 reverted the majority of altered mg44 -F2 expression levels to approximately wild-type values, although a substantial number of genes remained significantly distinct from wild-type, implying that age-1(mg44) modulates transcription through both DAF-16/FOXO-dependent and independent channels. When age-1 -inhibited genes were targeted by RNA interference (RNAi) in wild-type or age-1(hx546) adults, most conferred significant oxidative-stress protection. RNAi constructs targeting two of those genes were shown previously to extend life, and RNAi's targeting five novel genes were found here to increase lifespan. PI3K - null mutants may thus implicate novel mechanisms of life extension. [source] AtNAC2, a transcription factor downstream of ethylene and auxin signaling pathways, is involved in salt stress response and lateral root developmentTHE PLANT JOURNAL, Issue 6 2005Xin-Jian He Summary An NAC-type transcription factor gene AtNAC2 was identified from Arabidopsis thaliana when expression patterns of the genes from a microarray analysis were examined. The AtNAC2 expression was induced by salt stress and this induction was reduced in magnitude in the transgenic Arabidopsis plants overexpressing tobacco ethylene receptor gene NTHK1. AtNAC2 is localized in the nucleus and has transcriptional activation activity. It can form a homodimer in yeast. AtNAC2 was highly expressed in roots and flowers, but less expressed in other organs examined. In addition to the salt induction, the AtNAC2 can also be induced by abscisic acid (ABA), ACC and NAA. The salt induction was enhanced in the ethylene overproducer mutant eto1-1, but suppressed in the ethylene-insensitive mutants etr1-1 and ein2-1, and in the auxin-insensitive mutant tir1-1when compared with that in wild-type plants. However, the salt induction of AtNAC2 was not significantly affected in the ABA-insensitive mutants abi2-1, abi3-1 and abi4-1. These results indicate that the salt response of AtNAC2 requires ethylene signaling and auxin signaling pathways but does not require ABI2, ABI3 and ABI4, intermediates of the ABA signaling pathway. Overexpression of AtNAC2 in transgenic Arabidopsis plants resulted in promotion of lateral root development. AtNAC2 also promoted or inhibited downstream gene expressions. These results indicate that AtNAC2 may be a transcription factor incorporating the environmental and endogenous stimuli into the process of plant lateral root development. [source] A sensitized genetic background reveals evolution near the terminus of the Caenorhabditis germline sex determination pathwayEVOLUTION AND DEVELOPMENT, Issue 4 2009Robin Cook Hill SUMMARY Caenorhabditis elegans and Caenorhabditis briggsae are both self-fertile hermaphroditic nematodes that evolved independently from male/female ancestors. In C. elegans, FEM-1, FEM-2, and FEM-3 specify male fates by promoting proteolysis of the male-repressing transcription factor, TRA-1. Phenotypes of tra-1 and fem mutants are consistent with this simple linear model in the soma, but not in the germline. While both XX and XO tra-1(lf) mutants have functional male somas, they produce both sperm and oocytes. Further, all three tra-1; fem double mutants retain the expected male soma, but make only oocytes (the germline fem phenotype). Thus, a poorly characterized tra-1 activity is important for sustained male spermatogenesis, and the fem genes affect germline sexual fate independently of their role in regulating TRA-1. C. briggsae tra-1 mutants are phenotypically identical to their C. elegans counterparts, while the fem mutants differ in the germline: XX and XO C. elegans fem mutants are true females, but in C. briggsae they are self-fertile hermaphrodites. To further explore how C. briggsae hermaphrodites regulate germline sex, we analyzed Cb-tra-1/Cb-fem interactions. Cb-tra-1 is fully epistatic to Cb-fem-2 in the germline, unlike the orthologous C. elegans combination. In contrast, Cb-fem-3 shifts the Cb-tra-1(lf) germline phenotype to that of a nearly normal hermaphrodite in the context of a male somatic gonad. This suggests that Cb-fem-3 is epistatic to Cb-tra-1(lf) (as in C. elegans), and that the normal control of C. briggsae XX spermatogenesis targets Cb-tra-1 -independent factors downstream of Cb-fem-3. The effect of Cb-fem-3(lf) on Cb-tra-1(lf) is not mediated by change in the expression of Cb-fog-3, a likely direct germline target of Cb-tra-1. As Cb-fem-2 and Cb-fem-3 have identical single mutant phenotypes, Cb-tra-1 provides a sensitized background that reveals differences in how they promote male germline development. These results represent another way in which C. briggsae germline sex determination is incongruent with that of the outwardly similar C. elegans. [source] | ||||||||||