The Jun family members, c-Jun and JunD, transactivate the human c-myb promoter via an Ap1-like element.
The c-myb protooncogene, which is preferentially expressed in hematopoietic cells at the G1/S boundary of the cell cycle, encodes a transcriptional activator that functions via DNA binding. The regulatory mechanisms governing this specific pattern of expression are not fully understood, although human c-myb expression appears to be positively autoregulated via myb-binding sites in the 5'-flanking region of the c-myb gene (Nicolaides, N. C., Gualdi, R., Casadevall, C., Manzella, L., and Calabretta, B. (1991) Mol. Cell. Biol. 11, 6166-6176). To determine the contribution of other transcription regulators such as JUN family members in the control of c-myb expression, transient expression assays were carried out which revealed a 6- to a 15-fold enhancement by c-Jun and JunD, but not JunB, in chloramphenicol acetyltransferase reporter gene expression driven by different segments of the human c-myb 5'-flanking region. An Ap1-like element located at nucleotide -149 from the c-myb initiation site appears to be required for this transactivation upon binding to a nuclear protein complex containing c-Jun and JunD, since site-directed mutations of this Ap1-like element abolished c-Jun and JunD binding and transactivation. Exposure of phytohemagglutinin-stimulated peripheral blood mononuclear cells to c-jun and junD antisense oligodeoxynucleotides resulted in a 46 and 43% inhibition of T-lymphocyte proliferation that was accompanied by a decrease in c-myb mRNA levels as compared with sense-treated cultures. Because T-lymphocytes induced to proliferate express c-jun and junD before c-myb, these data suggest a mechanism whereby c-Jun and JunD contribute to the transcriptional activation of c-myb that, in turn, is maintained at the G1/S transition and during S phase by positive autoregulation.
Nicolaides
N C
NC
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19140.
Correa
I
I
Casadevall
C
C
Travali
S
S
Soprano
K J
KJ
Calabretta
B
B
D001483:Base Sequence; D016373:DNA, Antisense; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009857:Oncogenes; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000502:physiology; D015533:Transcriptional Activation
D016373:DNA, Antisense; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger