The role of autoproteolysis and mitoribosomal proteins in the regulation of the mitochondrial LACTB tumor suppressor.

Cancer cells in breast tumors exploit LACTB's autoproteolytic activity, leading to its self-degradation and inactivation, with LACTB's activity modulated by increased MRPS34 levels.

• Why it matters: Understanding post-translational mechanisms of tumor suppressor inactivation is crucial because they represent less explored pathways that cancer cells use to promote tumorigenesis beyond genetic or epigenetic changes.
• What they did: The study identified that LACTB can autoprocess itself and that breast cancer cells upregulate mitochondrial MRPS34, which interacts with LACTB to enhance its autoproteolytic activity and decrease LACTB levels.
• The result: This mechanism reveals how cancer cells regulate tumor suppressor activity through post-translational modifications, providing potential targets for restoring LACTB function in breast cancer therapy.