Differential Regulation of c-Jun and JunD by Ubiquitin-Dependent Protein Degradation

Musti, Anna Maria
Treier, Mathias
Peverali, Fiorenzo A.
Bohmann, Dirk

EMBL, Meyerhofstr. 1, D-69117 Heidelberg, Germany

^*Corresponding author

^aOn leave from: Centro di Endocrinologia ed Oncologia Sperimentale of CNR, Naples, Italy

^bPresent address: Howard Hughes Medical Institute, UC San Diego, La Jolla, CA 92093–0648, USA

Received August 6, 1996; accepted August 15, 1996

Biological Chemistry 377(10):p 619-624, October 1996.

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 δ-domain.