Human Papillomavirus Type 1 E1^E4 Protein Is a Potent Inhibitor of the Serine-Arginine (SR) Protein Kinase SRPK1 and Inhibits Phosphorylation of Host SR Proteins and of the Viral Transcription and Replication Regulator E2

摘要: The serine-arginine-specific protein kinase SRPK1 is a common binding partner of the E1^E4 diverse human papillomavirus types. We show here for first time that interaction between HPV1 and leads to potent inhibition phosphorylation host serine-arginine (SR) proteins have critical roles in mRNA metabolism, including pre-mRNA processing, export, translation. Furthermore, we phosphorylates serine residues SR/RS dipeptides hinge region E2 vitro assays inhibits this phosphorylation. After mutation putative phosphoacceptor residues, localization was altered primary keratinocytes; with significant increase cell population showing intense staining nucleolus. A similar effect observed following coexpression competent activity, suggesting nuclear sensitive E1^E4-mediated inhibition. Collectively, these data suggest could affect functions SR those virus transcription/replication regulator E2. speculate novel E4 function identified involved regulation posttranscriptional processing viral transcripts. IMPORTANCE HPV life cycle tightly linked epithelial terminal differentiation program, virion-producing phase restricted differentiating cells. While most abundant expressed protein, do not fully understand role protein. Few partners been identified, but had previously shown from papillomaviruses interact SRPK1, important replication cycles range DNA RNA viruses. inhibitor kinase. phosphorylation, only cellular regulating alternative splicing also Our findings reveal potential late gene expression through