title: The mitotic chromosome binding activity of the papillomavirus E2 protein correlates with interaction with the cellular chromosomal protein, Brd4.
abstract: The papillomavirus transcriptional activator, E2, is involved in key functions of the viral life cycle. These include transcriptional regulation, viral DNA replication, and viral genome segregation. The transactivation domain of E2 is required for each of these functions. To identify the regions of the domain that mediate binding to mitotic chromosomes, a panel of mutations has been generated and their effect on various E2 functions has been analyzed. A structural model of the bovine papillomavirus type 1 (BPV1) E2 transactivation domain was generated based on its homology with the solved structure of the human papillomavirus type 16 (HPV16) domain. This model was used to identify distinct surfaces of the domain to be targeted by point mutation to further delineate the functional region of the transactivation domain responsible for mitotic chromosome association. The mutated E2 proteins were assessed for mitotic chromosome binding and, in addition, transcriptional activation and transcriptional repression activities. Mutation of amino acids R37 and I73, which are located on a surface of the domain that in HPV16 E2 is reported to mediate self-interaction, completely eliminated mitotic chromosome binding. Mitotic chromosome binding activity was found to correlate well with the ability to interact with the cellular chromosomal associated factor Brd4, which has recently been proposed to mediate the association between BPV1 E2 and mitotic chromosomes.
authors.affiliation: Laboratory of Viral Diseases, NIAID, NIH, Building 4, Room 137, 4 Center Dr., MSC 0455, Bethesda, MD 20892-0455, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Baxter
authors.forename: Maria G
authors.initials: MG
authors.lastname: McPhillips
authors.forename: Keiko
authors.initials: K
authors.lastname: Ozato
authors.forename: Alison A
authors.initials: AA
authors.lastname: McBride
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D002455:Cell Division; D002877:Chromosomes, Human / Q000235:genetics; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000235:genetics*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism; D000092468:Bromodomain Containing Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D009856:Oncogene Proteins, Viral; D011994:Recombinant Proteins; D014157:Transcription Factors; D014764:Viral Proteins; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins; C051550:E2 protein, Bovine papillomavirus; C076036:oncogene protein E2, Human papillomavirus type 1