Epithelial CRL4DCAF2 is critical for mucosal repair in intestine

The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. An aberrant increase in the rate of intestinal epithelial cell (IEC) death underlies instances of extensive epithelial erosion, which is characteristic of several intestinal diseases such as inflammatory bowel disease(IBD) and infectious colitis. The E3 ligase CRL4DCAF2 is believed to be a pivotal regulator of the cell cycle. Here we found that DCAF2 expression was significantly decreased in UC patients. Mice with intestinal epithelial-specific knockout of DCAF2 might suffer from embryonic death. DCAF2 IEC-conditional knockdown mouse displayed more severe inflammation presentations in DSS-induced colitis model. Using transcriptomic approaches, we showed that CRL4DCAF2 in IECs regulates the intestine barriar and positively regulates DNA replication.CRL4DCAF2 promoted the proliferation of IEC. DCAF2 deficiency facilitated apoptosis protein accumulation .we also revealed that CRL4DCAF2 may reduce the symptoms of colitis by maintaining the stability of autophagy. MLN4924 treatment, which mimics DCAF2 depletion, also promotes the severity of mouse colitis models. This study shows that CRL4DCAF2 is crucial for intestine barriar stability and highlights a unique mechanism protein ubiquitination in the pathogenesis and development of IBD.