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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Nuclear proteasomal degradation of Saccharomyces cerevisiae inorganic pyrophosphatase Ipp1p, a nucleocytoplasmic protein whose stability depends on its subcellular localization

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Author(s):
Serrano-Bueno, Gloria [1, 2] ; Manuel Madronal, Juan [1] ; Manzano-Lopez, Javier [3] ; Muniz, Manuel [3, 4] ; Roman Perez-Castineira, Jose [1] ; Hernandez, Agustin [1, 5] ; Serrano, Aurelio [1]
Total Authors: 7
Affiliation:
[1] Univ Seville, CSIC, Inst Bioquim Vegetal & Fotosintesis, Av Amer Vespucio 49, Seville 41092 - Spain
[2] Univ Tecn Ambato, Fac Ciencia & Ingn Alimentos, Ambato 180103 - Ecuador
[3] Univ Seville, Dept Biol Celular, E-41012 Seville - Spain
[4] Univ Seville, Inst Biomed Sevilla IBIS, E-41012 Seville - Spain
[5] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, Av Lineu Prestes 1374, BR-05508000 Sao Paulo, SP - Brazil
Total Affiliations: 5
Document type: Journal article
Source: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH; v. 1866, n. 6, p. 1019-1033, JUN 2019.
Web of Science Citations: 1
Abstract

Inorganic pyrophosphate (PPi) is an abundant by-product of cellular metabolism. PPi-producing reactions take place in the nucleus concurrently with reactions that use PPi as a substrate. Saccharomyces cerevisiae possesses two soluble pyrophosphatases (sPPases): Ipp1p, an essential and allegedly cytosolic protein, and Ipp2p, a mitochondria) isoenzyme. However, no sPPase has yet been unambiguously described in the nucleus. In vivo studies with fluorescent fusions together with activity and immunodetection analyses demonstrated that Ipp1p is a nucleocytoplasmic protein. Mutagenesis analysis showed that this sPPase possesses a nuclear localization signal which participates in its nuclear targeting. Enforced nucleocytoplasmic targeting by fusion to heterologous nuclear import and export signals caused changes in polypeptide abundance and activity levels, indicating that Ipp1p is less stable in the nucleus that in the cytoplasm. Low nuclear levels of this sPPase are physiologically relevant and may be related to its catalytic activity, since cells expressing a functional nuclear-targeted chimaera showed impaired growth and reduced chronological lifespan, while a nuclear-targeted catalytically inactive protein was not degraded and accumulated in the nucleus. Moreover, nuclear proteasome inhibition stabilized Ipp1p whereas nuclear targeting promoted its ubiquitination and interaction with Ubp3p, a component of the ubiquitin-proteasome system. Overall, our results indicate that Ipp1p is nucleocytoplasmic, that its stability depends on its subcellular localization and that sPPase catalytic competence drives its nuclear degradation through the ubiquitin-proteasome system. This suggests a new scenario for PPi homeostasis where both nucleocytoplasmic transport and nuclear proteasome degradation of the sPPase should contribute to control nuclear levels of this ubiquitous metabolite. (AU)

FAPESP's process: 14/10443-0 - Mechanisms and consequences of intracellular traffic impairment by 8- and 14-dehydrosterols in fungal parasite models
Grantee:Agustín Hernández López
Support Opportunities: Research Grants - Young Investigators Grants