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Identification of the bZIP Transcription Factor Haclp as a Putative Target of the Mcklp Kinase of Yeast

机译:鉴定bZIP转录因子Haclp作为酵母Mcklp激酶的假定靶标

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摘要

The unfolded protein response (UPR) pathway is an evolutionarily conserved intracellular signal transduction pathway that functions to reduce the ER stress by increasing protein-folding capacity of the ER. A bZIP transcription factor Haclp functions in the UPR pathway in Saccharomyces cerevisiae. Haclp up-regulates the transcription of genes encoding ER-resident molecular chaperones and folding enzymes under ER stress conditions. Mcklp is a dual specificity protein kinase with multiple functions in meiotic progression, centromere activity and pyruvate kinase activity. In this study, Haclp was isolated as an Mcklp interacting protein in the yeast two-hybrid assay. The HAC1 two-hybrid clones were able to interact with both wild-type and kinase-deficient forms of Mcklp. Genetically, spliced form of Haclp suppresses the mck1 defect in IME1 expression. hac1 triangle open mutants display reduced sporulation efficiency phenotype characteristic of mckl A mutants. Furthermore, Hac1 triangle open can be phosphorylated by Mcklp in vitro suggesting that Mcklp might function as a regulator of Haclp. Under appropriate circumstances, mckl A mutants display a reduced degree of the UPR. We propose that Haclp is a putative target of the Mck1 triangle open and thatHAC1 and MCKL share functional specificity in yeast.
机译:未折叠的蛋白应答(UPR)途径是进化上保守的细胞内信号转导途径,其功能是通过增加ER的蛋白折叠能力来降低ER应激。 bZIP转录因子Haclp在酿酒酵母(Saccharomyces cerevisiae)的UPR途径中起作用。 Haclp上调内质网应激条件下编码内质网驻留分子伴侣和折叠酶的基因的转录。 Mcklp是一种双特异性蛋白激酶,在减数分裂进程,着丝粒活性和丙酮酸激酶活性中具有多种功能。在这项研究中,Haclp在酵母双杂交检测法中作为Mcklp相互作用蛋白被分离出来。 HAC1两个杂交克隆能够与野生型和激酶缺陷型的Mcklp相互作用。从基因上讲,Haclp的剪接形式抑制了IME1表达中的mck1缺陷。 hac1三角形开放突变体显示出降低的mckl A突变体的孢子形成效率表型。此外,Maclp可以在体外使Hac1三角形开放磷酸化,表明Mcklp可能充当Haclp的调节剂。在适当的情况下,mckl A突变体显示出降低的UPR程度。我们建议Haclp是Mck1三角形开放的假定目标,并且HAC1和MCKL在酵母中共享功能特异性。

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