The mechanism degrades short-lived proteins that support brain and immune functions Short-lived proteins control gene expression in cells and execute critical roles ranging from assisting brain connectivity to fortifying the body's immune response. Originating in the nucleus, these proteins are swi
Scientists have found a new way cells degrade unneeded proteins, which influence vital neural, immune, and developmental genes. This discovery may lead to treatments for conditions caused by protein imbalances in cells.Short-lived proteins control gene expression in cells and execute critical roles ranging from assisting brain connectivity to fortifying the body’s immune response. Originating in the nucleus, these proteins are swiftly degraded after fulfilling their purpose.
“The mechanism we found is very simple and quite elegant,” added co-lead author Christopher Nardone, a PhD candidate in genetics at HMS. “It is a basic science discovery, but there are many implications for the future.”It is well-established that cells can break down proteins by tagging them with a small molecule called ubiquitin. The tag tells the proteasome that the proteins are no longer needed, and it destroys them.
One group of proteins that seemed to be degraded by an alternative mechanism are stimuli-induced transcription factors: Proteins rapidly made in response to cellular stimuli that travel to the nucleus of a cell to turn on genes, after which they are rapidly destroyed. Gu and Nardone recall being shocked and skeptical about their results. To confirm their findings, they decided they needed to figure out exactly how midnolin targets and degrades so many different proteins.
“The most exciting aspect of this study is that we now understand a new general, ubiquitination-independent mechanism that degrades proteins,” Elledge said.In the short term, the researchers want to delve deeper into the mechanism they discovered. They are planning structural studies to better understand the fine-scale details of how midnolin captures and degrades proteins. They are also making mice that lack midnolin to understand the protein’s role in different cells and stages of development.
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Scientists discover a previously unknown way cells break down proteinsShort-lived proteins control gene expression in cells to carry out a number of vital tasks, from helping the brain form connections to helping the body mount an immune defense. These proteins are made in the nucleus and are quickly destroyed once they've done their job. The mechanism degrades short-lived proteins that support brain and immune functions.
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