Proteasomal interaction as a critical activity modulator of the human constitutive androstane receptor

In this study, we demonstrate that proteasomal inhibition markedly disrupts CAR function, repressing CAR nuclear trafficking, disrupting CAR’s interaction with nuclear co-activators and inhibiting induction of CAR target gene responses in human primary hepatocytes following treatment with either PB or CITCO. Paradoxically, these effects occur following accumulation of ubiquitinated hCAR and its interaction with the SUG1 subunit of the 26S proteasome. Together, these data demonstrate that the proteasome complex functions at multiple levels to regulate the functional biology of hCAR activity.

Source: BJ Cell - November 14, 2013 Category: Biochemistry Authors: T Chen, E M. Laurenzana, D M. Coslo, F Chen, C J. Omiecinski Tags: BJ Cell Source Type: research