Yun-Cai Liu, Ph.D and his team study the regulation of lymphocyte
function by tagging a small peptide ubiquitin to protein targets and
the implication of the ubiquitin system in abnormal immune responses
such as autoimmune diseases or allergic asthma.
The process of ubiquitin conjugation to a protein substrate is carried out by sequential enzymatic reactions. When a protein is tagged with ubiquitin, it sends a signal for destruction by the garbage disposal machinery inside the cell. Timely removal of harmful or excessive proteins is critical to maintain normal cell function. Dysfunction in this system can result in a disease state such as cancer, or immunological diseases.
Work from Dr. Liu's team has established that Cbl family of adaptor proteins acts as E3 ubiquitin ligases, which facilitate the transfer of ubiquitin to a specific protein target. More recent work identified that one of this family proteins, Cbl-b, is essential to keep T cells under control. Loss of Cbl-b results in excessive T cell activation, which leads to the attack of self-tissues or organs such as the joints or pancreas, and the development of arthritis and diabetes.
Dr. Liu's team also discovered that another E3 ubiquitin ligase, Itch, is a critical regulator for the development of a specific subset of T cells, called T cell helper type 2, which are responsible for the production of allergic mediators. Loss of Itch results in abnormal excessive function of these cells, and in the development of allergic asthma. Further understanding of the ubiquitin system may add in designing therapeutic inventions for human diseases such as arthritis, diabetes, and asthma.
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