The Jun family members, c-Jun and JunD, transactivate the human c-myb promoter via an Ap1-like element
Autor: | Nc Nicolaides, Bruno Calabretta, I Correa, Kj Soprano, C Casadevall, S Travali |
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Jazyk: | angličtina |
Rok vydání: | 1992 |
Předmět: |
Transcriptional Activation
JUNB Proto-Oncogene Proteins c-jun T-Lymphocytes Molecular Sequence Data Gene Expression Biology In Vitro Techniques Regulatory Sequences Nucleic Acid Lymphocyte Activation Biochemistry DNA Antisense DNA-Binding Proteins/physiology Chloramphenicol acetyltransferase Transactivation Humans RNA Messenger Molecular Biology Regulation of gene expression Reporter gene integumentary system Base Sequence fungi c-jun Cell Biology Oncogenes Molecular biology Proto-Oncogene Proteins c-jun/physiology DNA-Binding Proteins AP-1 transcription factor Gene Expression Regulation Oligodeoxyribonucleotides Regulatory sequence Protein Binding |
Zdroj: | Scopus-Elsevier |
Popis: | 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. |
Databáze: | OpenAIRE |
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