Pathways to the proteasome in yeast

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2023-12

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The proteasome is a highly selective and precisely regulated protease that degrades proteins essential for cellular homeostasis. This dissertation explores the molecular mechanisms by which the proteasome selects its substrates from a diverse protein pool First, the interplay between different pathways to the proteasome was investigated, revealing a hierarchy in degradation whereby substrates delivered by ubiquitin-like (UBL) domains may have priority access to the proteasome. Next, the role of spacing between the ubiquitin tag and disordered initiation region in degradation was investigated. The findings reveal another layer to substrate selection by the proteasome, and provide important considerations when determining whether a given protein may be degraded by the proteasome. Overall, this research provides new insights into how the proteasome selects its substrates in a diverse protein pool.

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