Adenovirus E1A specifically blocks SWI/SNF-dependent transcriptional activation.
Expression of the adenovirus E1A243 oncoprotein in Saccharomyces cerevisiae produces a slow-growth phenotype with accumulation of cells in the G1 phase of the cell cycle. This effect is due to the N-terminal and CR1 domains of E1A243, which in rodent cells are involved in triggering cellular transformation and also in binding to the cellular transcriptional coactivator p300. A genetic screen was undertaken to identify genes required for the function of E1A243 in S. cerevisiae. This screen identified SNF12, a gene encoding the 73-kDa subunit of the SWI/SNF transcriptional regulatory complex. Mutation of genes encoding known members of the SWI/SNF complex also led to loss of E1A function, suggesting that the SWI/SNF complex is a target of E1A243. Moreover, expression of E1A in wild-type cells specifically blocked transcriptional activation of the INO1 and SUC2 genes, whose activation pathways are distinct but have a common requirement for the SWI/SNF complex. These data demonstrate a specific functional interaction between E1A and the SWI/SNF complex and suggest that a similar interaction takes place in rodent and human cells.
Miller
M E
ME
Department of Microbiology, School of Medicine, University of Virginia Charlottesville 22908, USA.
Cairns
B R
BR
Levinson
R S
RS
Yamamoto
K R
KR
Engel
D A
DA
Smith
M M
MM
D017500:Adenovirus E1A Proteins / Q000096:biosynthesis / Q000502:physiology*; D000818:Animals; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D017931:DNA Primers; D029721:Drosophila Proteins; D016193:G1 Phase; D017353:Gene Deletion; D005800:Genes, Fungal; D005838:Genotype; D006801:Humans; D010641:Phenotype; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000235:genetics / Q000378:metabolism*; D012377:Rodentia; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D017500:Adenovirus E1A Proteins; D017931:DNA Primers; D029721:Drosophila Proteins; D016601:RNA-Binding Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; D014157:Transcription Factors; C089969:snf protein, Drosophila