TAF1 interacts with and modulates human papillomavirus 16 E2-dependent transcriptional regulation.
High-risk human papillomavirus (HPV) infection is the main etiological factor in the development of cervical cancer and viral type 16 is the most frequently found in this neoplasia. The E2 protein plays a key role in viral DNA replication, transcription and genome maintenance. E2 is a sequence-specific DNA-binding protein that activates or represses the transcriptional activity of promoters depending on the distance from the E2-binding sites to the TATA box. The transactivation properties of E2 are modulated by the interaction with several cellular factors that regulate the recruitment of transcription factor IID. Here, we demonstrate by pull-down assays the in vitro interaction of HPV16 E2 and TAF1. The domain of TAF1 necessary for the binding maps into its amino region, while the carboxy-terminal DNA-binding domain and the transactivation domain of the E2 protein are involved in the interaction. By transient cotransfection assays on C-33 A cells, we demonstrated that TAF1 enhances the activation of an E2-dependent artificial promoter while overexpression of TAF1 alleviates the E2-dependent repression of a high-risk HPV long control region. The specific modification of the transcriptional activity of both promoters by TAF1 suggests that the interaction between these proteins could participate in the modulation of the transregulatory properties of E2, with important biological consequences.
Centeno
Federico
F
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del IPN, México, D.F., México.
Ramírez-Salazar
Eric
E
García-Villa
Enrique
E
Gariglio
Patricio
P
Garrido
Efraín
E
D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D051548:Histone Acetyltransferases; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D035381:TATA-Binding Protein Associated Factors / Q000378:metabolism*; D035362:Transcription Factor TFIID / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D051548:Histone Acetyltransferases; C069001:TATA-binding protein associated factor 250 kDa