Novel Tripartite Motif Containing 22 Interactions in the Context of Very Early Onset Inflammatory Bowel Disease
Year: 2018
Type: dissertation
Abstract: Genetics predominate in very early onset inflammatory bowel disease (VEOIBD). With poor outcomes and therapeutic response, monogenic causes revealed by whole exome sequencing has potential for personalized therapies. Our recently published E3 ubiquitin ligase TRIM22 variants revealed novel roles in regulating NOD2. Apart from anti-viral pathways, the extent of TRIM22’s influence remains unclear. We interpreted TRIM22 BioID performed by collaborators. On the list of potential binding partners is the Nucleosome Remodeling and Deacetylase (NuRD) complex. Functional analysis shows TRIM22 binding HDAC1, the catalytic core of the NuRD complex, but may not ubiquitinate HDAC1 or alter its stability. VEOIBD variant TRIM22 R442C significantly reduces binding, and is the only variant to not form nuclear bodies. HDAC1 levels may be reduced in TRIM22 R321K patient pre-treatment colon biopsies. Given recent insights into TRIM22 mediated monocyte apoptosis, we suggest interaction with the NuRD complex plays a role in cell fate and inflammation.
Source: TSpace (University of Toronto)
Author: Khalid Hossain
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2942398415