The CtBP binding domain in the adenovirus E1A protein controls CR1-dependent transactivation.
The adenovirus E1A-243R protein has the ability to force a resting cell into uncontrolled proliferation by modulating the activity of key targets in cell cycle control. Most of these regulatory mechanisms are dependent on activities mapping to conserved region 1 (CR1) and the non-conserved N-terminal region of E1A. We have previously shown that CR1 functions as a very patent transactivator when it is tethered to a promoter through a heterologous DNA binding domain. However, artificial DNA binding was not sufficient to convert full-length E1A-243R to a transactivator. Thus, an additional function(s) of the E1A-243R protein modulates the effect of CR1 in transcription regulation. Here we demonstrate that a 44 amino acid region at the extreme C-terminus of ElA inhibited transactivation by a Gal4-CR1 fusion protein. Inhibition correlated with binding of the nuclear 48 kDa C-terminal binding protein (CtBP), which has been implicated in E1A-mediated suppression of the metastazing potential of tumour cells. This might suggest that CtBP binding can regulate E1A-mediated transformation by modulating CR1-dependent control of transcription.
Sollerbrant
K
K
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Chinnadurai
G
G
Svensson
C
C
D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D000429:Alcohol Oxidoreductases; D001665:Binding Sites; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; C084301:E1A protein 243R, Human adenovirus type 5; D010446:Peptide Fragments; D010750:Phosphoproteins; D012097:Repressor Proteins; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein