title: N-terminal acetylation and replicative age affect proteasome localization and cell fitness during aging.
abstract: Specific degradation of proteins is essential for virtually all cellular processes and is carried out predominantly by the proteasome. The proteasome is important for clearance of damaged cellular proteins. Damaged proteins accumulate over time and excess damaged proteins can aggregate and induce the death of old cells. In yeast, the localization of the proteasome changes dramatically during aging, possibly in response to altered proteasome activity requirements. We followed two key parameters of this process: the distribution of proteasomes in nuclear and cytosolic compartments, and the formation of cytoplasmic aggregate-like structures called proteasome storage granules (PSGs). Whereas replicative young cells efficiently relocalized proteasomes from the nucleus to the cytoplasm and formed PSGs, replicative old cells were less efficient in relocalizing the proteasome and had less PSGs. By using a microscopy-based genome-wide screen, we identified genetic factors involved in these processes. Both relocalization of the proteasome and PSG formation were affected by two of the three N-acetylation complexes. These N-acetylation complexes also had different effects on the longevity of cells, indicating that each N-acetylation complex has different roles in proteasome location and aging.
authors.affiliation: Division of Cell Biology, Netherlands Cancer Institute and Netherlands Proteomics Center, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
authors.forename: Sjoerd
authors.initials: S
authors.lastname: van Deventer
authors.affiliation: Division of Cell Biology, Netherlands Cancer Institute and Netherlands Proteomics Center, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
authors.forename: Victoria
authors.initials: V
authors.lastname: Menendez-Benito
authors.affiliation: Division of Gene Regulation, Netherlands Cancer Institute and Netherlands Proteomics Center, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
authors.forename: Fred
authors.initials: F
authors.lastname: van Leeuwen
authors.affiliation: Division of Cell Biology, Netherlands Cancer Institute and Netherlands Proteomics Center, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands j.neefjes@nki.nl.
authors.forename: Jacques
authors.initials: J
authors.lastname: Neefjes
mesh_terms: D000107:Acetylation; D003594:Cytoplasmic Granules / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D046988:Proteasome Endopeptidase Complex
keywords: Aging; Intracellular location; N-acetylation; Proteasome; Replicative age