Transformation by Fos proteins requires a C-terminal transactivation domain.
The Fos family of proteins now includes seven members: the retroviral proteins FBR-v-Fos and FBJ-v-Fos and the cellular proteins c-Fos, FosB, FosB2, Fra1, and Fra2. Four proteins (FBR-v-Fos, FBJ-v-Fos, c-Fos, and FosB) transform established rodent fibroblast cell lines, while three (FosB2, Fra1, and Fra2) do not. As all family members display sequence-specific DNA-binding activity as part of a heterodimeric complex with Jun proteins, other features must account for the differences in transforming potential. We demonstrate here that all transforming members have a C-terminal transactivation domain that is lacking in nontransforming members. The nontransforming proteins Fra1 and Fra2 can be converted to transforming proteins by fusion of a transactivation domain from either FosB or VP16. We also demonstrate that differences in the basic region-leucine zipper domain affecting either the affinity or sequence specificity of DNA binding are not determinants of the difference in transforming potential among members of the Fos family. The results further define the functional requirements for transformation by Fos proteins and suggest that the subunit composition of AP1 complexes is an important determinant of mitogenic signalling capability.
Wisdon
R
R
Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92186-5800.
Verma
I M
IM
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics; D016761:Oncogene Proteins v-fos / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012313:RNA / Q000235:genetics; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D015533:Transcriptional Activation; D014162:Transfection; D014170:Transformation, Genetic
D016761:Oncogene Proteins v-fos; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011965:Receptors, Glucocorticoid; D011993:Recombinant Fusion Proteins; D012313:RNA; D004247:DNA