Son Sunghun, Osmani Stephen A
Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA.
Eukaryot Cell. 2009 Apr;8(4):573-85. doi: 10.1128/EC.00346-08. Epub 2009 Jan 30.
Reversible protein phosphorylation is an important regulatory mechanism of cell cycle control in which protein phosphatases counteract the activities of protein kinases. In Aspergillus nidulans, 28 protein phosphatase catalytic subunit genes were identified. Systematic deletion analysis identified four essential phosphatases and four required for normal growth. Conditional alleles of these were generated using the alcA promoter. The deleted phosphatase strain collection and regulatable versions of the essential and near-essential phosphatases provide an important resource for further analysis of the role of reversible protein phosphorylation to the biology of A. nidulans. We further demonstrate that nimT and bimG have essential functions required for mitotic progression since their deletions led to classical G(2)- and M-phase arrest. Although not as obvious, cells with AnpphA and Annem1 deleted also have mitotic abnormalities. One of the essential phosphatases, the RNA polymerase II C-terminal domain phosphatase Anfcp1, was further examined for potential functions in mitosis because a temperature-sensitive Anfcp1 allele was isolated in a genetic screen showing synthetic interaction with the cdk1F mutation, a hyperactive mitotic kinase. The Anfcp1(ts) cdk1F double mutant had severe mitotic defects, including inability of nuclei to complete mitosis in a normal fashion. The severity of the Anfcp1(ts) cdk1F mitotic phenotypes were far greater than either single mutant, confirming the synthetic nature of their genetic interaction. The mitotic defects of the Anfcp1(ts) cdk1F double mutant suggests a previously unrealized function for AnFCP1 in regulating mitotic progression, perhaps counteracting Cdk1-mediated phosphorylation.
可逆性蛋白质磷酸化是细胞周期调控的一种重要调节机制,其中蛋白质磷酸酶可抵消蛋白激酶的活性。在构巢曲霉中,已鉴定出28个蛋白质磷酸酶催化亚基基因。系统缺失分析确定了4种必需磷酸酶和4种正常生长所需的磷酸酶。利用alcA启动子产生了这些磷酸酶的条件等位基因。缺失磷酸酶的菌株库以及必需和近乎必需磷酸酶的可调控版本为进一步分析可逆性蛋白质磷酸化在构巢曲霉生物学中的作用提供了重要资源。我们进一步证明,nimT和bimG具有有丝分裂进程所需的基本功能,因为它们的缺失导致经典的G2期和M期阻滞。虽然不太明显,但缺失AnpphA和Annem1的细胞也存在有丝分裂异常。对其中一种必需磷酸酶RNA聚合酶II C末端结构域磷酸酶Anfcp1在有丝分裂中的潜在功能进行了进一步研究,因为在一个遗传筛选中分离到了一个温度敏感型Anfcp1等位基因,该等位基因与cdk1F突变(一种活性过高的有丝分裂激酶)表现出合成相互作用。Anfcp1(ts) cdk1F双突变体具有严重的有丝分裂缺陷,包括细胞核无法以正常方式完成有丝分裂。Anfcp1(ts) cdk1F有丝分裂表型的严重程度远大于任一单突变体,证实了它们遗传相互作用的合成性质。Anfcp1(ts) cdk1F双突变体的有丝分裂缺陷表明AnFCP1在调节有丝分裂进程中具有以前未认识到的功能,可能是抵消Cdk1介导的磷酸化作用。