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Multi-purpose protein regulates new protein synthesis and immune cell development

A signaling protein called IRE1, which helps stressed-out cells make new proteins, may be more versatile and important than scientists believed. A new study by researchers from the University of Michigan Medical School and the Howard Hughes Medical Institute reveals the surprising finding that this same signaling protein is required for the formation of immune cells called B lymphocytes.

"This is a unique signaling pathway," says Randal Kaufman, Ph.D., a professor of biological chemistry in the U-M Medical School and an HHMI investigator. "In most pathways, there are multiple components and crosstalk. But there's only one IRE1 gene and one protein that carries out a unique biochemical reaction. This makes IRE1 a perfect target for pharmacological intervention for B cell-driven autoimmune diseases, like myasthenia gravis or systemic lupus erythematosus."

Results from the study will be published in the Feb. 1 issue of the Journal of Clinical Investigation.

Kaufman studies fundamental signaling pathways involved in the production of new proteins in the cell's endoplasmic reticulum (ER). The process begins with chains of amino acids, which are deposited in the ER membrane in response to coded instructions from genes. Chaperone proteins fold these amino acid chains into specific shapes and direct them to different areas of the ER for processing.

When too many amino acids pile up in the ER membrane, or when something goes wrong with the folding process, the entire system can get clogged with unfolded proteins. To prevent this, the cell activates the unfolded protein response (UPR).

"The UPR has three main aspects," Kaufman explains. "First, it signals the nucleus to stop synthesizing new proteins to give the ER time to catch up. Second, it induces expression and synthesis of more chaperone proteins to assist with protein folding and help with protein trafficking. And third, it activates genes involved in protein degradation
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Source:University of Michigan Health System


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