Mar 23, 2020

Mechanisms of up-regulation of Ubiquitin-Proteasome activity in the absence of NatA dependent N-terminal acetylation

BioRxiv : the Preprint Server for Biology
I. KatsMichael Knop

Abstract

N-terminal acetylation is a prominent protein modification and inactivation of N-terminal acetyltransferases (NATs) cause protein homeostasis stress. Using multiplexed protein stability (MPS) profiling with linear ubiquitin fusions as reporters for the activity of the ubiquitin proteasome system (UPS) we observed increased UPS activity in NatA, but not NatB or NatC mutants. We find several mechanisms contributing to this behavior. First, NatA-mediated acetylation of the N-terminal ubiquitin independent degron regulates the abundance of Rpn4, the master regulator of the expression of proteasomal genes. Second, the abundance of several E3 ligases involved in degradation of UFD substrates is increased in cells lacking NatA. Finally, we identify the E3 ligase Tom1 as a novel chain elongating enzyme (E4) involved in the degradation of linear ubiquitin fusions via the formation of branched K11 and K29 ubiquitin chains, independently of the known E4 ligases involved in UFD, leading to enhanced ubiquitination of the UFD substrates.

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Mentioned in this Paper

Biological Markers
Treatment Protocols
Size
Research
Mutagenicity Tests
Neoplasms
Cancer Progression
Deleterious Mutation
Genomics
Adaptation

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