The carboxyterminus of human c-myb protein stimulates activated transcription in trans.
The cellular c-myb gene encodes a transcription factor composed of a DNA-binding domain, a transactivating domain and a regulatory domain located at its carboxy (C-) terminus. The latter one is deleted in the transforming viral protein v-Myb. Here we show that deletion of the C-terminus of c-Myb increases the transcriptional transactivation activity of c-Myb defining it as cis-acting negative regulatory domain. Cotransfection of the C-terminus in an in vivo competition assay causes stimulation of the transcriptional activity of various v- and c-Myb expression constructs in trans. The effect is dose-dependent and independent of the kind of DNA-binding domain, since c-Myb as well as GAL4-c-Myb chimaeras can be stimulated in trans. Other transcription factors, such as GAL4-VP16, GAL4, c-Jun or C/EBP beta are also stimulated by the cotransfected C-terminus. In contrast, human B-Myb is not stimulated by the c-Myb C-terminus in trans. The data suggest that the C-terminus of c-Myb may interact with a cellular inhibitor which is part of the protein complex mediating activated transcription and may stimulate in trans by sequestering away such an inhibitor. Binding of c-Myb to a putative inhibitor would explain differences between c-Myb in comparison to B- and v-Myb in transcriptional regulation.
Vorbrueggen
G
G
Max-Planck-Institut für Molekulare Genetik, Abteilung Schuster, Berlin, Germany.
Kalkbrenner
F
F
Guehmann
S
S
Moelling
K
K
D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C064352:MYBL2 protein, human; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors