Project title: Regulation and control of linear ubiquitin chian synthesis: Structure, function and mechanism of linear ubiquitin chian assembly complex LUBAC
Summary: The linear ubiquitin chain assembly complex LUBAC is E3 ubiquitin ligase that plays pivotal roles in the innitiation of innate and adpative immune response, especially in the activation of nuclear factor-kappa B, which is a transcription factor that induces transcription of inflammatory genes. Abberrant LUBAC activity has been known as a contributor to diffuse large B-cell lymphoma (DLBL), which is a bone marrow malignancy. More importantly, individuals carrying congenital mutaions in LUBAC protein domains (i.e. HOIP, HOIL-1, SHARPIN) manifest devastating immunodeficiency and/or autoinflammatory symptoms. All those add up to the fact that LUBAC is really interesting and important. This project aims to unveal regulatory mechanisms for LUBAC activity with aid from biochemical and structural biology techiniques (i.e. in vitro protein expression, gene cloning, column chromatography, and X-ray crystallography etc.).