Fig. 4

Ubiquitination and degradation of HBO1. HBO1 can undergo ubiquitination by the SCF (SKP1/Cullin-1/Fbxw15) and CRL4 (DDB1-CUL4A-RBX1) complexes. Protein kinase MEK1 phosphorylates HBO1, promoting its degradation via the Fbxw15-mediated ubiquitin proteasome pathway. In mouse lung epithelial cells (MLE-12), LPS induces HBO1 degradation through this pathway. Conversely, LPS stimulation in THP-1 monocytes and human primary macrophages inhibits HBO1 ubiquitination by increasing the level of deubiquitinase USP25 protein, resulting in varying degrees of HBO1 protein elevation. Furthermore, DNA damage caused by UV irradiation leads to the degradation of HBO1 by the DDB2-mediated CRL4 (DDB1–CUL4A–RBX1) complex