Phorbol ester-induced amino-terminal phosphorylation of human JUN but not JUNB regulates transcriptional activation.

AUTOR(ES)

Franklin, C C

RESUMO

Phorbol ester tumor promoters activate gene transcription by regulating both the synthesis and posttranslational modification of the activator protein 1 (AP-1) transcription factor, c-Jun and JunB are components of the mammalian AP-1 complex. Here we demonstrate that in U-937 human leukemic cells, phorbol esters stimulate the phosphorylation of the amino terminus of human c-Jun (JUN) but not human JunB (JUNB). Mutational analysis indicates that serine-63 and -73, which reside within the putative regulatory domain of JUN, are required for both constitutive and phorbol 12-myristate 13-acetate-inducible N-terminal JUN phosphorylation. To determine the functional role of this N-terminal phosphorylation, we prepared several chimeric proteins containing the N-terminal 84 amino acids (positions 5-89) of human JUN or murine JUNB fused to the yeast GAL4 DNA-binding domain. This region was found to be sufficient for the phorbol ester-inducible transcriptional activity of JUN, but not JUNB. This induction was abolished by the mutation of serine-63 and -73 to leucine residues. Thus, we propose that phorbol esters enhance the trans-activation potential of JUN, but not JUNB, by the phosphorylation of the N-terminal regulatory domain of JUN.

Documentos Relacionados

• Phorbol ester-induced stimulation and phosphorylation of adenylyl cyclase 2.
• Upstream regions of the c-jun promoter regulate phorbol ester-induced transcription in U937 leukemic cells.
• B-Cell Receptor- and Phorbol Ester-Induced NF-κB and c-Jun N-Terminal Kinase Activation in B Cells Requires Novel Protein Kinase C's
• Phorbol ester-induced terminal differentiation is inhibited in human U-937 monoblastic cells expressing a v-myc oncogene.
• Phorbol ester-induced synaptic facilitation is different than long-term potentiation.