title: The transcription factors TBX2 and TBX3 interact with human papillomavirus 16 (HPV16) L2 and repress the long control region of HPVs.
abstract: The minor capsid protein L2 of human papillomaviruses (HPVs) has multiple functions during the viral life cycle. Although L2 is required for effective invasion and morphogenesis, only a few cellular interaction partners are known so far. Using yeast two-hybrid screening, we identified the transcription factor TBX2 as a novel interaction partner of HPV type 16 (HPV16) L2. Coimmunoprecipitations and immunofluorescence analyses confirmed the L2-TBX2 interaction and revealed that L2 also interacts with TBX3, another member of the T-box family. Transcription of the early genes during HPV infection is under the control of an upstream enhancer and early promoter region, the long control region (LCR). In promoter-reporter gene assays, we observed that TBX2 and TBX3 repress transcription from the LCR and that this effect is enhanced by L2. Repression of the HPV LCR by TBX2/3 seems to be a conserved mechanism, as it was also observed with the LCRs of different HPV types. Finally, interaction of TBX2 with the LCR was detected by chromatin immunoprecipitation, and we found a strong colocalization of L2 and TBX2 in HPV16-positive cervical intraepithelial neoplasia (CIN) I-II tissue sections. These results suggest that TBX2/3 might play a role in the regulation of HPV gene expression during the viral life cycle.
authors: Department of Microbiology and Hygiene, University Medical Center of Johannes Gutenberg University Mainz, Mainz, Germany.
authors: Marc A
authors: MA
authors: Schneider
authors: Konstanze D
authors: KD
authors: Scheffer
authors: Timo
authors: T
authors: Bund
authors: Fatima
authors: F
authors: Boukhallouk
authors: Carsten
authors: C
authors: Lambert
authors: Cristina
authors: C
authors: Cotarelo
authors: Gert O
authors: GO
authors: Pflugfelder
authors: Luise
authors: L
authors: Florin
authors: Gilles A
authors: GA
authors: Spoden
mesh_terms: D036022:Capsid Proteins / Q000378:metabolism*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D025941:Protein Interaction Mapping; D020825:T-Box Domain Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D014779:Virus Replication
chemical_list: D036022:Capsid Proteins; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; C106884:TBX3 protein, human
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