c-Jun localizes to the nucleus independent of its phosphorylation by and interaction with JNK and vice versa promotes nuclear accumulation of JNK

• Published in: Biochemical and biophysical research communications Vol. 407; no. 4; pp. 735 - 740
• Main Authors: Schreck, Ilona, Al-Rawi, Marco, Mingot, José-Manuel, Scholl, Christine, Diefenbacher, Markus Elmar, O’Donnell, Paul, Bohmann, Dirk, Weiss, Carsten
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.04.2011
• Subjects: 60 APPLIED LIFE SCIENCES; ABUNDANCE; ANIMAL CELLS; Antigens, Nuclear - metabolism; APOPTOSIS; beta Karyopherins - metabolism; BUILDUP; c-Jun; Cell Nucleus - metabolism; DIMERIZATION; DNA; DNA DAMAGES; DNA-Binding Proteins - metabolism; HEAT-SHOCK PROTEINS; HEK293 Cells; Humans; JNK; Ku Autoantigen; MAP Kinase Kinase 4 - genetics; MAP Kinase Kinase 4 - metabolism; PHOSPHORYLATION; Protein Structure, Tertiary; Proto-Oncogene Proteins c-jun - genetics; Proto-Oncogene Proteins c-jun - metabolism; Signaling; Transcription factor; TRANSCRIPTION FACTORS; TRANSLOCATION; c-Jun; Signaling; Transcription factor; JNK
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.03.092

► HSP70, Ku70 and 80 as well as importin 8 are novel interactors of c-Jun. ► Nuclear accumulation of c-Jun does not require its functions as a transcription factor. ► Nuclear accumulation of c-Jun does not require the interaction with its kinase JNK. ► Nuclear accumulation of JNK is regulated by interaction with c-Jun. In order to activate gene expression, transcription factors such as c-Jun have to reside in the nucleus. The abundance of c-Jun in the nucleus correlates with the activity of its target genes. As a consequence of excessive c-Jun activation, cells undergo apoptosis or changes in differentiation whereas decreased c-Jun function can reduce proliferation. In the present study we addressed how nuclear accumulation of the transcription factor c-Jun is regulated. First, we analyzed which functions of c-Jun are required for efficient nuclear accumulation. Mutants of c-Jun deficient in dimerization or DNA-binding show no defect in nuclear transport. Furthermore, c-Jun import into the nucleus of living cells occurred when the c-Jun phosphorylation sites were mutated as well in cells that lack the major c-Jun kinase, JNK, suggesting that c-Jun transport into the nucleus does not require JNK signaling. Conversely, however, binding of c-Jun seemed to enhance nuclear accumulation of JNK. In order to identify proteins that might be relevant for the nuclear translocation of c-Jun we searched for novel binding partners by a proteomic approach. In addition to the heat shock protein HSP70 and the DNA damage repair factors Ku70 and 80, we isolated human importin 8 as a novel interactor of c-Jun. Interaction of Imp 8 with c-Jun in human cells was confirmed by co-immunoprecipitation experiments. Nuclear accumulation of c-Jun does not require its functions as a transcription factor or the interaction with its kinase JNK. Interestingly, nuclear accumulation of JNK is regulated by interaction with c-Jun. Unraveling the mechanisms of c-Jun and JNK transport to the nucleus and its regulation will improve our understanding of their role in biological and pathophysiological processes.