| Description |
Protein degradation in cells is a complex network of pathways that are distinct from each other but highly interconnected. Understanding how proteins are degraded in cells is important for understanding and developing treatments for diseases such as lysosomal storage diseases and neurodegenerative diseases caused by the toxic accumulation of proteins. To better characterize the interplay between protein degradation pathways we began by researching how and why the degradation pathway followed by misfolded proteins generated during stress changes from unstressed cells. Misfolded proteins that occasionally arise in the cell are degraded by the proteasome; a protein based cellular structure responsible for the degradation of many proteins. However, if the number of misfolded proteins in a cell increases, they begin to be degraded by lysosomes, membrane bound acidic organelles. We hypothesized proteasome function could be a signal for when the cell needs to use additional or alternative pathways for degradation. We tested the functionality of the proteasome with the Ubiquitin Fusion Degradation (UFD) Reporter protein, which allows live cell measurements of proteasome function based on fluorescent levels of the UFD protein. The results of this test showed that the proteasome is partially functional when cells are treated with chemicals that induce protein misfolding in the endoplasmic reticulum. Therefore, proteasome function could be a signal for use of other degradation pathways to degrade proteins during times of stress. Additionally, we found the UFD protein is degraded by a co-occurring lysosome dependent pathway. Our findings demonstrate that lysosome and proteasome degradation pathways are intricately connected, and partially compensate for each other during stress. |
