A novel, transformation-relevant activation domain in Fos proteins.
We have previously demonstrated that transformation by Fos is critically dependent on an intact DNA-binding domain (bZip) and a functional N-terminal transactivation motif (N-TM). We now show that a novel motif (C-terminal transactivation motif [C-TM]) near the C terminus also plays an important role in both transformation and the activation of AP1-dependent transcription and that the hydrophobic amino acids in the C-TM are functionally essential. The C-TM is the most crucial element in the C-terminal transactivation domain in Fos, as indicated by its relative strength and context-independent function. The C-TM is clearly different from the previously identified HOB2 domain, located N terminally to the C-TM, and the C-terminally positioned TATA-binding protein-binding domain. We also show that the C-terminal transactivation domain strongly synergizes with the HOB1-like N-TM, even when both domains are present on different proteins within a dimeric complex, and that the C-TM plays a crucial role in this cooperation. These observations can be corroborated in a model in which multiple contacts with the basal machinery are established either to stabilize the transcription complex or to facilitate its sequential assembly.
Funk
M
M
Institut für Molekularbiologie und Tumorforschung, Phillips-Universität Marburg, Germany.
Poensgen
B
B
Graulich
W
W
Jerome
V
V
Müller
R
R
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D016762:Genes, fos / Q000235:genetics; D005816:Genetic Complementation Test; D051379:Mice; D008969:Molecular Sequence Data; D008980:Moloney murine sarcoma virus; D009154:Mutation; D014411:Neoplastic Stem Cells; D016761:Oncogene Proteins v-fos / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D051381:Rats; D011993:Recombinant Fusion Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics*
D016761:Oncogene Proteins v-fos; D016760:Proto-Oncogene Proteins c-fos; D011993:Recombinant Fusion Proteins