Pleiotropic roles of the Msi1-like protein Msl1 in Cryptococcus neoformans.
Pleiotropic roles of the Msi1-like protein Msl1 in Cryptococcus neoformans.
复制标题
Msi1 样蛋白 Msl1 在新型隐球菌中的多效性作用。
DOI：
10.1128/ec.00261-12
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Bahn,Yong-Sun
中科院分区：
文献类型：
--
作者：
Yang,Dong-Hoon;Maeng,Shinae;Strain,AnnaK;Floyd,Anna;Nielsen,Kirsten;Heitman,Joseph;Bahn,Yong-Sun
Msi 1-like（MSIL）蛋白含有WD 40基序，并且作为Ras/环AMP（cAMP）途径的负调节剂和染色质组装因子1（CAF-1）的组分具有多效性细胞功能，但它们尚未在真菌病原体中进行研究。在这里，我们确定并表征了一种MSIL蛋白，MSL 1，在新型隐球菌，这会导致危及生命的脑膜脑炎的人类。值得注意的是，Msl 1在C.在cAMP依赖性和非依赖性的方式在很大程度上独立于Ras的新生儿。Msl 1负控制抗氧化剂黑色素的产生和性分化，这是抑制cAMP信号通路的抑制。相比之下，Msl 1控制耐热性，不同的应激反应，并在Ras/cAMP独立的方式抗真菌药物耐药性。与Msl 1的功能相比，作为第二CAF-1组分的Cac 2似乎发挥冗余和不同的功能。Msl 1是C.新人类转录组分析确定了一组受Msl 1调控的基因，其中包括应激相关基因如HSP 12和HSP 78。总之，这项研究表明，在人类真菌病原体C。neoformans，提供了一个潜在的新的抗真菌治疗靶点的见解。
Msi1-like (MSIL) proteins contain WD40 motifs and have a pleiotropic cellular function as negative regulators of the Ras/cyclic AMP (cAMP) pathway and components of chromatin assembly factor 1 (CAF-1), yet they have not been studied in fungal pathogens. Here we identified and characterized an MSIL protein, Msl1, in Cryptococcus neoformans, which causes life-threatening meningoencephalitis in humans. Notably, Msl1 plays pleiotropic roles in C. neoformans in both cAMP-dependent and -independent manners largely independent of Ras. Msl1 negatively controls antioxidant melanin production and sexual differentiation, and this was repressed by the inhibition of the cAMP-signaling pathway. In contrast, Msl1 controls thermotolerance, diverse stress responses, and antifungal drug resistance in a Ras/cAMP-independent manner. Cac2, which is the second CAF-1 component, appears to play both redundant and distinct functions compared to the functions of Msl1. Msl1 is required for the full virulence of C. neoformans. Transcriptome analysis identified a group of Msl1-regulated genes, which include stress-related genes such asHSP12andHSP78. In conclusion, this study demonstrates pleiotropic roles of Msl1 in the human fungal pathogen C. neoformans, providing insight into a potential novel antifungal therapeutic target.