Fig. 4. COP1 outcompetes CSN to assemble the CRL4^COP1 E3 ligase for ETV5 degradation in Csn2^WT/K70E (Het) mice and in response to nutrients.

a Structural models illustrating steric incompatibility between COP1 and CSN. For modeling details, see “Methods”. b Effect of COP1 and DET1 overexpression, individually or combined, on CRL–CSN complex formation in MIN6 cells. c, d CRL4–COP1 complex formation detected by COP1 co-immunoprecipitation with Cul4A (c) and Cul4B (d) from WT and Csn2^WT/K70E pancreas lysates. e Effect of adding IP₆ (20 μM) into MIN6 cell lysates on CRL4B^COP1 complex formation. f Glucose fasting (2 h) increases CSN3-Cul4B co-ip in MIN6 cells, which is reversed by replacement with glucose-proficient medium (1 h). g Glucose fasting (2 h) decreases Cul4B-CSN3 co-ip in MIN6 cells, which is reversed by replacement with glucose-proficient medium (1 h).