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Bre1 and Ubp8 regulate H2B mono‐ubiquitination and the reversible yeast‐hyphae transition in Candida albicans
Molecular Microbiology ( IF 2.6 ) Pub Date : 2020-10-03 , DOI: 10.1111/mmi.14619
Wencheng Zhu 1 , Xueyi Fan 1 , Qun Zhao 1 , Yinxing Xu 1 , Xiongjun Wang 1 , Jiangye Chen 1
Affiliation  

The reversible yeast‐hyphae transition of the human fungal pathogen Candida albicans is tightly linked to its pathogenicity. In this study, we show that histone H2B mono‐ubiquitination (H2Bub) at lysine 123 was maintained at a low level in the yeast state, whereas it increased significantly during yeast‐to‐hyphae transition and decreased when hyphae converted to yeast. The increased H2Bub level is correlated with activation of the hyphal program. H2B ubiquitination and deubiquitination are dynamically regulated by the E3 ligase Bre1 and the deubiquitinase Ubp8 during the reversible yeast‐hyphae transition. The functions of Bre1 and Ubp8 in hypha‐specific gene (HSG) regulation appears to be direct because both are recruited to the coding regions of HSGs during hyphal induction. The sequential recruitment of Bre1 and Ubp8 to HSGs coding regions is important for the initiation and maintenance of HSG expression. Additionally, Ubp8 contributes to the pathogenicity of C. albicans during early infection in a mouse model. Our study is the first to link H2B ubiquitination to the morphological plasticity and pathogenicity of the human fungal pathogen C. albicans and shed light on potential antifungal treatments.

中文翻译:

Bre1 和 Ubp8 调节 H2B 单泛素化和白色念珠菌的可逆酵母菌丝转化

人类真菌病原体白色念珠菌的可逆酵母菌转变与其致病性密切相关。在这项研究中,我们表明,赖氨酸 123 的组蛋白 H2B 单泛素化 (H2Bub) 在酵母状态下保持在较低水平,而在酵母菌向菌丝过渡期间显着增加,而在菌丝转化为酵母时则减少。增加的 H2Bub 水平与菌丝程序的激活相关。H2B 泛素化和去泛素化在酵母菌菌丝可逆转变期间由 E3 连接酶 Bre1 和去泛素化酶 Ubp8 动态调节。Bre1 和 Ubp8 在菌丝特异性基因 (HSG) 调控中的功能似乎是直接的,因为它们在菌丝诱导过程中都被募集到 HSG 的编码区。Bre1 和 Ubp8 向 HSG 编码区的顺序募集对于 HSG 表达的启动和维持很重要。此外,小鼠模型早期感染期间的白色念珠菌。我们的研究首次将 H2B 泛素化与人类真菌病原体白色念珠菌的形态可塑性和致病性联系起来,并阐明了潜在的抗真菌治疗方法。
更新日期:2020-10-03
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