Publikation: FAT10 and NUB1L cooperate to activate the 26S proteasome
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The homeostasis of proteins including protein synthesis, proper folding, post-translational modifications (PTM) as well as recycling and degradation of proteins is an essential aspect of cellular life. The proteasome plays a key role by degrading short-lived, misfolded, and damaged proteins within cells. It is known that the ATP-dependent degradation of intracellular proteins is caused by the 76-amino acid polypeptide ubiquitin. Another PTM, fatylation, means covalent attachment of the ubiquitin like protein FAT10 (HLA-F adjacent transcript 10), serves in a similar way and guides labeled proteins are degraded by the proteasome. The interaction of the 19S regulatory particle of the 26S proteasome with ubiquitylated proteins leads to gate opening of the 20S core particle and increases its proteolytic activity by displacing the inhibitory deubiquitylation enzyme USP14 from the 19S regulator subunit RPN1. Covalent modification with the cytokine inducible ubiquitin-like modifier FAT10 is an alternative signal for proteasomal degradation. In this thesis, it is shown that FAT10 and its interaction partner NUB1L facilitate the gate opening of the 20S proteasome in a ubiquitin- and USP14-independent manner. It is also demonstrated, that monomeric FAT10 is capable to activate all peptidolytic activities of the 26S proteasome exclusively in interplay with NUB1L by binding to the UBA-domains of NUB1L and thereby interfering with NUB1L dimerization. The binding of FAT10 to NUB1L increases the affinity of NUB1L for the subunit RPN1. In conclusion, the herein described cooperation of FAT10 and NUB1L is a substrate-induced mechanism to activate the 26S proteasome.
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BROCKMANN, Florian, 2023. FAT10 and NUB1L cooperate to activate the 26S proteasome [Dissertation]. Konstanz: Universität KonstanzBibTex
@phdthesis{Brockmann2023FAT10-72086, title={FAT10 and NUB1L cooperate to activate the 26S proteasome}, year={2023}, author={Brockmann, Florian}, address={Konstanz}, school={Universität Konstanz} }
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