Department of Biological Chemistry, University of California, Irvine, California 92697, USA.
Nat Commun. 2016 Oct 3;7:12916. doi: 10.1038/ncomms12916.
N-acetylglucosamine (GlcNAc) exists ubiquitously as a component of the surface on a wide range of cells, from bacteria to humans. Many fungi are able to utilize environmental GlcNAc to support growth and induce cellular development, a property important for their survival in various host niches. However, how the GlcNAc signal is sensed and subsequently transduced is largely unknown. Here, we identify a gene that is essential for GlcNAc signalling (NGS1) in Candida albicans, a commensal and pathogenic yeast of humans. Ngs1 can bind GlcNAc through the N-terminal β-N-acetylglucosaminidase homology domain. This binding activates N-acetyltransferase activity in the C-terminal GCN5-related N-acetyltransferase domain, which is required for GlcNAc-induced promoter histone acetylation and transcription. Ngs1 is targeted to the promoters of GlcNAc-inducible genes constitutively by the transcription factor Rep1. Ngs1 is conserved in diverse fungi that have GlcNAc catabolic genes. Thus, fungi use Ngs1 as a GlcNAc-sensor and transducer for GlcNAc-induced transcription.
N-乙酰葡萄糖胺（GlcNAc）作为一种广泛存在于各种细胞表面的成分，从细菌到人类都存在。许多真菌能够利用环境中的 GlcNAc 来支持生长并诱导细胞发育，这一特性对于它们在各种宿主小生境中的生存至关重要。然而，GlcNAc 信号是如何被感知并随后转导的，在很大程度上仍然未知。在这里，我们鉴定了一种在白色念珠菌中对 GlcNAc 信号至关重要的基因（NGS1），白色念珠菌是一种人类共生和致病酵母。Ngs1 可以通过 N 端β-N-乙酰氨基葡萄糖苷酶同源结构域结合 GlcNAc。这种结合激活了 C 端 GCN5 相关 N-乙酰转移酶结构域中的 N-乙酰转移酶活性，这对于 GlcNAc 诱导的启动子组蛋白乙酰化和转录是必需的。Ngs1 由转录因子 Rep1 持续靶向 GlcNAc 诱导基因的启动子。Ngs1 在具有 GlcNAc 分解代谢基因的各种真菌中是保守的。因此，真菌利用 Ngs1 作为 GlcNAc 传感器和转导子来诱导 GlcNAc 诱导的转录。
