AI Article Synopsis
- The study focuses on Ppz1, a protein phosphatase from the yeast Saccharomyces cerevisiae, which is known for its toxicity when overexpressed and is regulated by two subunits, Hal3 and Vhs3.
- Researchers found that the toxicity associated with excessive Ppz1 expression is linked to its increased phosphatase activity rather than affecting coenzyme A biosynthesis.
- They identified ribosomal proteins and assembly factors as potential suppressors of Ppz1 toxicity and suggested that Ppz1's overexpression disrupts normal protein synthesis, indicated by changes in eIF2α phosphorylation.
Article Abstract
The Ser/Thr protein phosphatase Ppz1 from Saccharomyces cerevisiae is the best characterized member of a family of enzymes only found in fungi. Ppz1 is regulated in vivo by two inhibitory subunits, Hal3 and Vhs3, which are moonlighting proteins also involved in the decarboxylation of the 4-phosphopantothenoylcysteine (PPC) intermediate required for coenzyme A biosynthesis. It has been reported that, when overexpressed, Ppz1 is the most toxic protein in yeast. However, the reasons for such toxicity have not been elucidated. Here we show that the detrimental effect of excessive Ppz1 expression is due to an increase in its phosphatase activity and not to a plausible down-titration of the PPC decarboxylase components. We have identified several genes encoding ribosomal proteins and ribosome assembly factors as mild high-copy suppressors of the toxic Ppz1 effect. Ppz1 binds to ribosomes engaged in translation and copurifies with diverse ribosomal proteins and translation factors. Ppz1 overexpression results in Gcn2-dependent increased phosphorylation of eIF2α at Ser-51. Consistently, deletion of GCN2 partially suppresses the growth defect of a Ppz1 overexpressing strain. We propose that the deleterious effects of Ppz1 overexpression are in part due to alteration in normal protein synthesis.
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| http://dx.doi.org/10.1016/j.bbamcr.2020.118727 | DOI Listing |
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Article Synopsis
- Overexpression of the yeast Ser/Thr protein phosphatase Ppz1 significantly halts cell proliferation, with recent research revealing the underlying molecular mechanisms.
- Changes in gene expression and alterations in the phosphorylation state of over 150 proteins, including important kinases like Hog1 and Snf1, contribute to diverse cellular disruptions.
- The toxic effects of excess Ppz1 are countered by overexpression of its regulatory subunit Hal3, which leads to the relocation of Ppz1 to internal membranes, mitigating the growth blockage.
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