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

Christopher C. Franklin, Veronica Sanchez, Fred Wagner, James R. Woodgett, Andrew S. Kraft

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7247-7251
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number15
DOIs
StatePublished - Jan 1 1992
Externally publishedYes

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