Exploring the complexity of protein-level dosage compensation that fine-tunes stoichiometry of multiprotein complexes

• Verfasst von: Ishikawa, Koji [VerfasserIn]
• Verfasst von: Ishihara, Akari [VerfasserIn]
• Verfasst von: Moriya, Hisao [VerfasserIn]
• Titel: Exploring the complexity of protein-level dosage compensation that fine-tunes stoichiometry of multiprotein complexes
• Verf.angabe: Koji Ishikawa, Akari Ishihara, Hisao Moriya
• E-Jahr: 2020
• Jahr: October28, 2020
• Fussnoten: Gesehen am 18.01.2021
• Titel Quelle: Enthalten in: Public Library of SciencePLoS Genetics
• Ort Quelle: San Francisco, Calif. : Public Library of Science, 2005
• Jahr Quelle: 2020
• Band/Heft Quelle: 16(2020,10) Artikel-Nummer e1009091, 21 Seiten
• ISSN Quelle: 1553-7404
• DOI: doi:10.1371/journal.pgen.1009091
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1744889937

Abstract

Proper control of gene expression levels upon various perturbations is a fundamental aspect of cellular robustness. Protein-level dosage compensation is one mechanism buffering perturbations to stoichiometry of multiprotein complexes through accelerated proteolysis of unassembled subunits. Although N-terminal acetylation- and ubiquitin-mediated proteasomal degradation by the Ac/N-end rule pathway enables selective compensation of excess subunits, it is unclear how widespread this pathway contributes to stoichiometry control. Here we report that dosage compensation depends only partially on the Ac/N-end rule pathway. Our analysis of genetic interactions between 18 subunits and 12 quality control factors in budding yeast demonstrated that multiple E3 ubiquitin ligases and N-acetyltransferases are involved in dosage compensation. We find that N-acetyltransferases-mediated compensation is not simply predictable from N-terminal sequence despite their sequence specificity for N-acetylation. We also find that the compensation of Pop3 and Bet4 is due in large part to a minor N-acetyltransferase NatD. Furthermore, canonical NatD substrates histone H2A/H4 were compensated even in its absence, suggesting N-acetylation-independent stoichiometry control. Our study reveals the complexity and robustness of the stoichiometry control system.