New Insights into a Protein Critical for B-Cell Cancers

Researchers at UT Southwestern Medical Center have made significant progress in understanding a protein called midnolin, which plays a vital role in the survival and proliferation of malignant B cells involved in various blood cancers such as leukemias, lymphomas, and multiple myelomas. Using advanced cryo-electron microscopy technology, the team determined the detailed structure of midnolin, revealing how it functions within cells.

The study, published in the Proceedings of the National Academy of Sciences (PNAS), uncovers a novel ubiquitin-independent pathway through which midnolin interacts with proteasomes—cellular machinery responsible for degrading unneeded or damaged proteins. Unlike typical proteins degraded via ubiquitin tagging, midnolin carries proteins directly to proteasomes, stimulating their activity without the usual tagging process. Structural images highlighted critical areas of midnolin that enable this unique interaction, with one resembling ubiquitin, which helps open the gateway in proteasomes for protein disposal.

This discovery is particularly promising because current therapies for B-cell cancers often involve proteasome inhibitors, which can cause severe side effects such as nerve damage, gastrointestinal issues, and bleeding risks. Since midnolin is mostly found in B cells, targeting its specific actions could lead to more precise and safer treatment options, potentially reducing the adverse effects associated with current proteasome-targeted drugs.

Lead researcher Dr. Nagesh Peddada explained that understanding midnolin’s structure and function could guide the development of new drugs that offer effective cancer treatment with fewer complications. The research team aims to further explore how drugs that modulate midnolin might serve as safer alternatives to existing proteasome inhibitors.

This breakthrough not only enhances the understanding of protein regulation in immune cells but also opens new avenues for therapeutic interventions in B-cell malignancies, emphasizing the importance of structural biology in medical research.

Source: medicalxpress.com