Welcome to the Joazeiro lab!

E3 ubiquitin ligases: roles in signaling, protein quality control, and disease

Broadly we are interested in the E3 ubiquitin ligases –their biological functions, mechanism of action, and roles in disease. For the past few years, we have focused on the problem of how cells know when its proteins are aberrant or damaged, and then decide on ways to either correct or eliminate them. Protein quality control is critical to ensure proteome integrity and cellular fitness; further underscoring its relevance, defective protein quality control is a hallmark of neurodegenerative diseases.

In eukaryotic organisms, key factors conferring specificity to protein quality control are molecular chaperones and E3 ligases. We have recently discovered a novel protein quality control mechanism mediated by an E3 ligase, Listerin/Ltn1, and which takes place on ribosomes. We now know that Listerin functions as a subunit of the Ribosome-Associated Quality Control (RQC) complex, which is conserved from yeast to humans. Of relevance, Listerin mutation causes motor neuron degeneration in mice.

We employ diverse model systems and approaches to elucidate how RQC-mediated quality control occurs at the cellular and molecular levels, including biochemistry, yeast genetics, cell biology, mouse models of neurodegeneration, and structural biology. We also analyze patients’ genomes to identify mutations that affect protein quality control; these studies are leading to insights onto the molecular basis of Amyotrophic Lateral Sclerosis (ALS) and other neurodegenerative diseases, and to potential therapeutic targets.

For additional information, please see our lab website at www.joazeirolab.com