Publications by authors named "Galen Andrew Collins"
Article Synopsis
- Ddi2, a shuttling factor in vertebrates, binds to ubiquitin (Ub) conjugates via its Ub-like domain, unlike its yeast counterparts that have a Ub-associated domain.
- Deleting Ddi2 results in the accumulation of Ub conjugates due to reduced binding to the proteasome, which impairs protein degradation.
- The protease activity of Ddi2 is crucial for its function in delivering Ub proteins to the proteasome, influencing protein turnover and potentially preventing stress in the endoplasmic reticulum.
Although ubiquitination is widely assumed to be the only regulated step in the ubiquitin-proteasome pathway, recent studies have demonstrated several important mechanisms that regulate the activities of the 26S proteasome. Most proteasomes in cells are inactive but, upon binding a ubiquitinated substrate, become activated by a two-step mechanism requiring an association of the ubiquitin chain with Usp14 and then a loosely folded protein domain with the ATPases. The initial activation step is signaled by Usp14's UBL domain, and many UBL-domain-containing proteins (e.
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- Proteasomes are crucial for protein degradation in mammalian cells, and their structure and function are important for maintaining cellular balance and understanding diseases.
- Inhibitors of proteasome activity are being explored for research and treatment, particularly in blood cancers, while new drugs that modify proteasome function are under development.
- To fully grasp how proteasomes work, various methods to measure their activities are crucial, providing insights into how they are regulated and their role in neurodegenerative diseases, surpassing traditional assays focused solely on peptidase activity.
Article Synopsis
- The text discusses three methods for isolating 26S proteasomes, which are important for studying how their activity and composition change in various conditions, including diseases and drug responses.
- The first method involves using affinity tags on proteasome subunits for advanced techniques like cryo-electron microscopy and mass spectrometry to analyze structure and composition.
- The second method relies on the proteasome's natural affinity for a ubiquitin-like domain for purification without tagged subunits, while the third method uses differential centrifugation to concentrate proteasomes based on their large size, preserving their functional associations.
Article Synopsis
- * New findings show that the proteasome itself plays a critical role in deciding whether a tagged protein gets destroyed or can survive longer, emphasizing its regulatory function.
- * This article discusses advancements in understanding how the proteasome works, including its energy-dependent processes, structural features for efficient protein breakdown, and how its activity is modified by interacting proteins and phosphorylation.