Alcohols inhibit translation to regulate morphogenesis in C. albicans.
Alcohols inhibit translation to regulate morphogenesis in C. albicans.
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DOI：
10.1016/j.fgb.2015.03.008
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发表时间：
2015-04
影响因子：
3
通讯作者：
Ashe, Mark P.
中科院分区：
文献类型：
--
作者：
Egbe, Nkechi E.;Paget, Caroline M.;Wang, Hui;Ashe, Mark P.
酒精可引起白色念珠菌的形态改变。酒精会抑制蛋白质的合成。翻译抑制是eIF2B调控的结果。蛋白质合成的调节和形态发生在机械上是联系在一起的。许多分子被微生物分泌到生长介质中，以调节生物体的代谢和生理过程。例如，丁醇、乙醇和异戊醇等酒精是由人类致病真菌白色念珠菌产生的，并诱导形态分化。在这里，我们展示了这些相同的醇导致蛋白质合成的快速抑制。更具体地说，酒精的目标是翻译启动，这是基因表达过程的一个复杂阶段。利用分子技术，我们已经确定了这些醇在白念珠菌中可能的翻译靶点是真核细胞翻译起始因子2B(EIF2B)。EIF2B是eIF2的鸟嘌呤核苷酸交换因子，它支持eIF2.GDP转化为eIF2.GTP的交换反应。即使在这一步骤中最小的调控也会导致特定蛋白质水平的变化，这可能使真菌的迫切需要得以实现。事实上，与酒精的影响类似，放线菌酮对蛋白质合成的最小抑制也会导致丝状生长的诱导。这些结果提示了不同醇对白念珠菌形态分化的影响的分子基础。
Alcohols induce morphological alterations in C. albicans. Alcohols inhibit protein synthesis. Translational inhibition occurs as a result of eIF2B regulation. Regulation of protein synthesis and morphogenesis are mechanistically connected. Many molecules are secreted into the growth media by microorganisms to modulate the metabolic and physiological processes of the organism. For instance, alcohols like butanol, ethanol and isoamyl alcohol are produced by the human pathogenic fungus, Candida albicans and induce morphological differentiation. Here we show that these same alcohols cause a rapid inhibition of protein synthesis. More specifically, the alcohols target translation initiation, a complex stage of the gene expression process. Using molecular techniques, we have identified the likely translational target of these alcohols in C. albicans as the eukaryotic translation initiation factor 2B (eIF2B). eIF2B is the guanine nucleotide exchange factor for eIF2, which supports the exchange reaction where eIF2.GDP is converted to eIF2.GTP. Even minimal regulation at this step will lead to alterations in the levels of specific proteins that may allow the exigencies of the fungus to be realised. Indeed, similar to the effects of alcohols, a minimal inhibition of protein synthesis with cycloheximide also causes an induction of filamentous growth. These results suggest a molecular basis for the effect of various alcohols on morphological differentiation in C. albicans.
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影响因子：
4.8
作者：
Dickinson, JR;Eshantha, L;Hewlins, MJE
通讯作者：
Hewlins, MJE
DOI：
10.1111/j.1432-1033.1993.tb17827.x
发表时间：
1993-04-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
DEHOUX, P;DAVIES, J;CANNON, M
通讯作者：
CANNON, M
DOI：
10.1073/pnas.0401416101
发表时间：
2004-04-06
影响因子：
11.1
作者：
Chen, H;Fujita, M;Fink, GR
通讯作者：
Fink, GR
DOI：
10.1099/13500872-142-6-1391
发表时间：
1996-06-01
期刊：
MICROBIOLOGY-UK
影响因子：
--
作者：
Dickinson, JR
通讯作者：
Dickinson, JR
影响因子：
2.1
作者：
Csank, C;Haynes, K
通讯作者：
Haynes, K