title: Involvement of Brd4 in different steps of the papillomavirus life cycle.
abstract: Bromodomain-containing protein 4 (Brd4) is a cellular chromatin-binding factor and transcriptional regulator that recruits sequence-specific transcription factors and chromatin modulators to control target gene transcription. Papillomaviruses (PVs) have evolved to hijack Brd4's activity in order to create a facilitating environment for the viral life cycle. Brd4, in association with the major viral regulatory protein E2, is involved in multiple steps of the PV life cycle including replication initiation, viral gene transcription, and viral genome segregation and maintenance. Phosphorylation of Brd4, regulated by casein kinase II (CK2) and protein phosphatase 2A (PP2A), is critical for viral gene transcription as well as E1- and E2-dependent origin replication. Thus, pharmacological agents regulating Brd4 phosphorylation and inhibitors blocking phospho-Brd4 functions are promising candidates for therapeutic intervention in treating human papillomavirus (HPV) infections as well as associated disease.
authors.affiliation: Division of Experimental Virology, Institute for Medical Virology, University Hospital Tübingen, Elfriede-Aulhorn-Str. 6, 72076 Tübingen, Germany. Electronic address: Thomas.Iftner@med.uni-tuebingen.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Iftner
authors.affiliation: Division of Experimental Virology, Institute for Medical Virology, University Hospital Tübingen, Elfriede-Aulhorn-Str. 6, 72076 Tübingen, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Haedicke-Jarboui
authors.affiliation: Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA; Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Shwu-Yuan
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA; Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. Electronic address: cheng-ming.chiang@utsouthwestern.edu.
authors.forename: Cheng-Ming
authors.initials: CM
authors.lastname: Chiang
mesh_terms: D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000821:virology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D027383:Papillomaviridae / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014779:Virus Replication; D000092468:Bromodomain Containing Proteins
chemical_list: D047390:Casein Kinase II; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D054648:Protein Phosphatase 2; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins; C054855:E2 protein, Human papillomavirus type 16
keywords: Brd4; E2 protein; Papillomavirus life cycle; Papillomavirus replication; Papillomavirus transcription