Department of Molecular Microbiology & Genetics, University of Goettingen, Goettingen, Germany.
Goettingen Center for Molecular Biosciences (GZMB), University of Goettingen, Goettingen, Germany.
PLoS Genet. 2018 Feb 5;14(2):e1007141. doi: 10.1371/journal.pgen.1007141. eCollection 2018 Feb.
The transition from vegetative growth to multicellular development represents an evolutionary hallmark linked to an oxidative stress signal and controlled protein degradation. We identified the Sem1 proteasome subunit, which connects stress response and cellular differentiation. The sem1 gene encodes the fungal counterpart of the human Sem1 proteasome lid subunit and is essential for fungal cell differentiation and development. A sem1 deletion strain of the filamentous fungus Aspergillus nidulans is able to grow vegetatively and expresses an elevated degree of 20S proteasomes with multiplied ATP-independent catalytic activity compared to wildtype. Oxidative stress induces increased transcription of the genes sem1 and rpn11 for the proteasomal deubiquitinating enzyme. Sem1 is required for stabilization of the Rpn11 deubiquitinating enzyme, incorporation of the ubiquitin receptor Rpn10 into the 19S regulatory particle and efficient 26S proteasome assembly. Sem1 maintains high cellular NADH levels, controls mitochondria integrity during stress and developmental transition.
从营养生长到多细胞发育的转变代表了与氧化应激信号和受控蛋白质降解相关的进化标志。我们鉴定了 Sem1 蛋白酶体亚基，它连接应激反应和细胞分化。sem1 基因编码人类 Sem1 蛋白酶体盖亚基的真菌对应物，对于真菌细胞分化和发育是必需的。丝状真菌构巢曲霉的 sem1 缺失菌株能够进行营养生长，并表达出比野生型更高程度的 20S 蛋白酶体，具有倍增的 ATP 非依赖性催化活性。氧化应激诱导蛋白酶体去泛素化酶的基因 sem1 和 rpn11 的转录增加。Sem1 对于 Rpn11 去泛素化酶的稳定、泛素受体 Rpn10 掺入 19S 调节颗粒以及高效 26S 蛋白酶体组装都是必需的。Sem1 维持高细胞 NADH 水平，在应激和发育转变期间控制线粒体完整性。
