Differential regulation of c-Jun and JunD by ubiquitin-dependent protein degradation

c-Jun and JunD are two closely related members of the Jun family of transcription factors which markedly differ in their biological functions. Whereas c-Jun behaves as a positive regulator of cell growth and may cause cell transformation when overexpressed, JunD antagonizes both of these effects. To better understand how the activities of c-Jun and JunD are controlled, we investigated how their stabilities within the cell are determined. We show that, in contrast to c-Jun which is degraded following multi ubiquitination, JunD is not efficiently ubiquitinated and exhibits a correspondingly longer half-life. Mutational analysis reveals that the determinant for the difference in ubiquitination resides in the NH2-terminal regions of the proteins which in c-Jun contains the delta-domain.