Carboxy-terminal elements of c-Myb negatively regulate transcriptional activation in cis and in trans.
The c-Myb protein plays a key role in normal hematopoiesis, and truncation results in its activation to a transforming protein. Truncation of the c-Myb carboxyl terminus also greatly increases its transcriptional activating activity. The role of specific carboxy-terminal domains in negative regulation was investigated using Myb and Myb fusions with GAL4, LexA, or VP16. Negative regulatory activity of the carboxyl terminus in cis resides in at least two regions. A sequence in one of these regions can also inhibit transcriptional activation by Myb, Myb-VP16, or LexA-Myb proteins in trans. Regulation in trans, or suppression, is independent of c-Myb DNA binding and, therefore, likely involves protein-protein interaction. Suppression does not require the presence of a predicted heptad leucine repeat structure on either molecule. The target of suppression is a sequence that contains part of the minimal Myb transcriptional activation domain. This sequence can confer suppressibility on fusion proteins containing heterologous DNA-binding or transcriptional activation domains.
Dubendorff
J W
JW
Department of Microbiology, School of Medicine, State University of New York at Stony Brook 11794-8621.
Whittaker
L J
LJ
Eltman
J T
JT
Lipsick
J S
JS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002645:Chickens; D004247:DNA; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D020626:Oncogene Proteins v-myb; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb; D011784:Quail; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013489:Suppression, Genetic; 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; D004247:DNA