Cullin 4b-RING ubiquitin ligase targets IRGM1 to regulate Wnt signaling and intestinal homeostasis.

ABSTRACT: Hierarchical organization of intestine relies on the self-renewal and tightly regulated differentiation of intestinal stem cells (ISCs). Although signals like Wnt are known to sustain the continued intestinal renewal by maintaining ISCs activity and lineage commitment, molecular mechanisms underlying ISCs 'stemness' and supportive niche have not been well understood. Here, we found that CUL4B-RING ubiquitin ligase (CRL4B) regulates intestinal homeostasis by targeting immunity-related GTPase family M member 1 (IRGM1) for proteasomal degradation. CUL4B was mainly expressed at ISCs zone. Deletion of Cul4b led to reduced self-renewal of ISCs and a decreased lineage differentiation towards secretory progenitors through downregulated Wnt signals. Besides, Cul4b-null mice exhibited impaired Panet

SUBMITTER: Fan Y 

PROVIDER: S-EPMC9433385 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature