Human Diseases and Ubiquitination

Ubiquitin is an essential amino acid protein that modifies other proteins in eukaryotes. These modifications, or ubiquitination, play an essential role in a broad number of cellular processes, including transcription, DNA repair, signal transduction, autophagy, cell cycle, immune response, and membrane trafficking. It follows that aberration in the mechanisms of ubiquitination can lead to a number of human diseases—specifically, neurodegenerative diseases and cancers.

Yuxin Mao, Molecular Biology and Genetics, has discovered one way that bacteria target and manipulate these essential processes and is working to uncover the precise molecular mechanisms.

Remarkably, although ubiquitin is absent in prokaryotes, bacteria can deliver certain ligases—bacterial pathogen-encoded E3 ubiquitin Ligases (BELs)—into eukaryotic host cells to manipulate the host ubiquitin system for successful infection. Mao’s lab recently discovered a novel family of BELs, named SidC, from the intracellular bacterial pathogen Legionella pneumophila. Ligases in the SidC family have a very unique sequence and structure, which raises intriguing questions: Given this structure, what is the molecular mechanism of this family of ligases? What are the specific substrates of SidC? And how does the ubiquitination of these potential host factors play a role in membrane trafficking regulation?

Mao’s lab is working to answer these questions. The results will make significant contributions to the understanding of both the molecular mechanisms of the enzymatic cascade of ubiquitination and the role of the host ubiquitin pathway in bacterial pathogenesis. These studies will therefore forge new trails in understanding human pathogens and will help combat bacterial infectious diseases. NIH Award Number: 1R01GM116964-01A1

Cornell Researchers

Funding Received

$1.2 Million spanning 4 years

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