Kelch-like protein 25

Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex involved in various processes, such as translation homeostasis and lipid synthesis. The BCR(KLHL25) ubiquitin ligase complex acts by mediating ubiquitination of hypophosphorylated EIF4EBP1 (4E-BP1): ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) probably serves as a homeostatic mechanism to maintain translation and prevent eIF4E inhibition when eIF4E levels are low. The BCR(KLHL25) complex does not target EIF4EBP1 (4E-BP1) when it is hyperphosphorylated or associated with eIF4E. The BCR(KLHL25) complex also acts as a regulator of lipid synthesis by mediating ubiquitination and degradation of ACLY, thereby inhibiting lipid synthesis. BCR(KLHL25)-mediated degradation of ACLY promotes fatty acid oxidation and is required for differentiation of inducible regulatory T (iTreg) cells.