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.
Musti
A M
AM
EMBL, Heidelberg, Germany.
Treier
M
M
Peverali
F A
FA
Bohmann
D
D
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D051379:Mice; D008969:Molecular Sequence Data; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism*
D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D014452:Ubiquitins