The carboxy-terminal domain of c-Myb activates reporter gene expression in yeast.
We have shown previously that c-myb expressed in the yeast S. cerevisiae mediated efficient transcriptional activation of reporter genes designed with specific Myb Recognition Elements (MRE's), confirming that this proto-oncogene is able to function as a regulator of transcription in that heterologous context. Here we show that in yeast, as in higher eucaryotic cells, the central domain of c-Myb displays transactivating capacity. In yeast, however, the carboxy-terminal region, defined as a negative regulatory domain in higher cells, activates transcription as well and appears to be a more potent transactivating domain than the central domain itself. Within this region two domains, namely C1 and C2, have been defined that contribute about equally to the activity of the carboxy-terminal region. C1 spans the sequences missing in AMV v-myb while C2, which contains the leucine-zipper motif is specifically absent in the E26 v-myb in addition to C1. The c-Myb DNA-binding domain itself has no effect on the level of transcription in yeast. We also show that AMV v-Myb stimulates gene expression in yeast with about half the efficiency of full length c-Myb. The fact that the carboxy-terminal region either stimulates or inhibits transactivation properties of c-Myb, depending on the cellular context, stresses the participation of putative c-Myb partner proteins in Myb regulated processes and reopens the question of whether the oncogenic activation of c-myb is indeed due to the increased transactivation capacity of its onco derivatives.
Seneca
S
S
Erfelijheidsleer en Microbiologie, Vrije Universiteit Brussel, Research Institute Ceria-Coovi, Belgium.
Punyammalee
B
B
Sureau
A
A
Perbal
B
B
Dvorák
M
M
Crabeel
M
M
D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D020626:Oncogene Proteins v-myb; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb; D015183:Restriction Mapping; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry* / Q000235:genetics; D012441:Saccharomyces cerevisiae; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D020626:Oncogene Proteins v-myb; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015682:Retroviridae Proteins, Oncogenic