NRIP enhances HPV gene expression via interaction with either GR or E2

We previously identified a gene, nuclear receptor-interaction protein (NRIP), which functions as a transcription cofactor in glucocorticoid receptor (GR) and human papillomavirus E2 (HPV E2)-driven gene expression. Here, we comprehensively evaluated the role of NRIP in HPV-16 gene expression. NRIP acts as a transcription cofactor to enhance GR-regulated HPV-16 gene expression in the presence of hormone. NRIP also can form complex with E2 that caused NRIP-induced HPV gene expression via E2-binding sites in a hormone-independent manner. Furthermore, NRIP can associate with GR and E2 to form tri-protein complex to activate HPV gene expression via GRE, not the E2-binding site, in a hormone-dependent manner. These results indicate that NRIP and GR are viral E2-binding proteins and that NRIP regulates HPV gene expression via GRE and/or E2 binding site in the HPV promoter in a hormone-dependent or independent manner, respectively.

► NRIP enhances GR-regulated HPV-16 gene expression in the presence of hormone.
► NRIP enhances E2-induced HPV gene expression in a hormone-independent manner.
► NRIP, GR and E2 can form tri-protein complex to activate HPV gene expression.
► The tri-protein complex stimulates HPV gene expression in hormone-dependent.
► Both NRIP and GR are E2-binding host factors to regulate HPV gene expression.