Affiliation:
1. Division of Gene Therapy and Regulation of Gene Expression, Centre for Applied Medical Research CIMA, University of Navarra, 31008 Pamplona, Spain
2. Department of Biology, Centre of Molecular and Environmental Biology (CBMA/UM), University of Minho, 4710-057 Braga, Portugal
Abstract
Alpha-aminoterminal acetyltransferase B (NatB) is a critical enzyme responsible for acetylating the aminoterminal end of proteins, thereby modifying approximately 21% of the proteome. This post-translational modification impacts protein folding, structure, stability, and interactions between proteins which, in turn, play a crucial role in modulating several biological functions. NatB has been widely studied for its role in cytoskeleton function and cell cycle regulation in different organisms, from yeast to human tumor cells. In this study, we aimed to understand the biological importance of this modification by inactivating the catalytic subunit of the NatB enzymatic complex, Naa20, in non-transformed mammal cells. Our findings demonstrate that depletion of NAA20 results in decreased cell cycle progression and DNA replication initiation, ultimately leading to the senescence program. Furthermore, we have identified NatB substrates that play a role in cell cycle progression, and their stability is compromised when NatB is inactivated. These results underscore the significance of N-terminal acetylation by NatB in regulating cell cycle progression and DNA replication.
Funder
ISCIII Consolidation Program Grant (R.A.), Ministerio Español de Economía y Competitividad Torres Quevedo Program
Departamento de Desarrollo Económico del Gobierno de Navarra
Fundación para la Investigación Médica Aplicada
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Cited by
2 articles.
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