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The Ser\/Thr protein phosphatase Ppz1 from\u00a0Saccharomyces cerevisiae<\/em>\u00a0is the best characterized member of a family of enzymes only found in fungi. Ppz1 is regulated\u00a0in vivo<\/em>\u00a0by 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 eIF2\u03b1 at Ser-51. Consistently, deletion of\u00a0GCN2<\/em>\u00a0partially 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.<\/p>\nHighlights<\/h2>\n\n
\n- \u2022High catalytic activity of Ppz1 is detrimental for cell growth.<\/dt>\n
- \u2022Overexpression of Ppz1 leads to Gcn2-dependent phosphorylation of eIF2\u03b1.<\/dt>\n
- \u2022Ppz1 interacts with ribosomal components.<\/dt>\n
- \u2022Excess of Ppz1 activity negatively affect the translation initiation process.<\/dt>\n
- <\/dt>\n<\/dl>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"
doi:10.1016\/j.bbamcr.2020.118727 Abstract The Ser\/Thr protein phosphatase Ppz1 from\u00a0Saccharomyces cerevisiae\u00a0is the best characterized member of a family of enzymes only found in fungi. Ppz1 is regulated\u00a0in vivo\u00a0by 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 […]<\/p>\n","protected":false},"author":65,"featured_media":3536,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[4],"tags":[],"_links":{"self":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts\/3534"}],"collection":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/users\/65"}],"replies":[{"embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/comments?post=3534"}],"version-history":[{"count":4,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts\/3534\/revisions"}],"predecessor-version":[{"id":3540,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts\/3534\/revisions\/3540"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/media\/3536"}],"wp:attachment":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/media?parent=3534"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/categories?post=3534"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/tags?post=3534"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
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