RT Journal Article
T1 Overexpression of budding yeast protein phosphatase Ppz1 impairs translation.
A1 Calafi, Carlos
A1 Lopez-Malo, Maria
A1 Velazquez, Diego
A1 Zhang, Chunyi
A1 Fernandez-Fernandez, Jose
A1 Rodriguez-Galan, Olga
A1 de-la-Cruz, Jesus
A1 Ariño, Joaquin
A1 Casamayor, Antonio
K1 Ppz1
K1 Protein phosphatase
K1 Ribosomal proteins
K1 Translation initiation
K1 Yeast
AB 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.
PB Elsevier BV
SN 0167-4889
YR 2020
FD 2020-04-24
LK http://hdl.handle.net/10668/15443
UL http://hdl.handle.net/10668/15443
LA en
NO Calafí C, López-Malo M, Velázquez D, Zhang C, Fernández-Fernández J, Rodríguez-Galán O, et al. Overexpression of budding yeast protein phosphatase Ppz1 impairs translation. Biochim Biophys Acta Mol Cell Res. 2020 Aug;1867(8):118727.
DS RISalud
RD Sep 28, 2025