| The papillomavirus E2 protein is a site-specific DNA binding nuclear protein functioning in both viral replication and transcription. In replication, E2 is the primary origin recognition protein and helps to recruit the replication initiator protein, E1. In transcription, E2 is the transcription factor responsible for regulation of the cellular transforming protein, E6, which at high concentrations can ultimately lead to cancer. E2 also helps to ensure viral genome segregation during mitosis. In order for E2 to perform all these functions, it needs to be imported into the nucleus after it is newly synthesized in the cytoplasm of an infected cell. This project investigated the nuclear import of high-risk HPV16 E2. We found that HPV16 E2 contains a nuclear localization signal located in the C terminus of the protein. Deletion of this sequence inhibited the protein from entering the nucleus in vivo. This cNLS, as well as the full-length protein, showed a specific interaction with Karyopherin alpha2, a known import adapter that interacts with Karyopherin beta1 import receptor, which is known to import proteins via the Kapalpha2beta 1 heterodimer complex nuclear import pathway. These data confirm that this cNLS is a functional and essential NLS of HPV16 E2. |
