Study on the functional interaction between human papillomavirus E2 and BRCA1

Abstract

The papillomavirus E2 protein binds as a dimer to its cognate sequence $(ACCN_6GGT)$ and is involved in viral transcription and DNA replication. Analysis of the amino acid sequences of various E2 proteins shows that E2 shares well-conserved domains, such as the amino-terminus of the transactivation domain and the carboxy terminus of the DNA binding domain. The transcriptional activation function of E2 is important for its regulation of host cell cycle, as well as for the regulation of viral gene transcription and DNA replication. It has previously shown that E2 interacts with several host factors which is involved in transcriptional regulation, including basic transcription factors and co-activators such as AMF-1/Gps2, p300, and CBP to exert its function as transcriptional activator. BRCA1 was first identified as a breast and ovarian cancer-related tumor suppressor and has been studied intensively for its role in damaged DNA repair and double-srand break-induced recombination. However, a growing body of evidence points toward a function of BRCA1 in transcriptional regulation in recent years. Two viewpoints regarding the function of BRCA1 have emerged. When tethered to a transcriptional promoter via a heterologous DNA binding domain, the C-terminal 304 amino acid region (residues 1560-1863) including the BRCT repeats can act as a trans-activation domain. It has been also reported that, when over-expressed in mammalian cells, the full-length BRCA1 protein can potentiate transcription from several natural promoters in a p53-dependent manner. In recent studies it was demonstrated that BRCA1 can interact with transcriptional activator p53 and ATF1 and act as a transcriptional co-activator, which is significant for the regulation of cell cycle or cell death by p53. To examine that there was some functional interaction between BRCA1 and E2, we performed the transient transcription assay. We show here that BRCA1 enhances human papillomavirus type 18 (HPV-18) E2-depen...