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Virus Details


VHFID4965

Host Factor Information

Pathogen Information

Publication Information

Host Factor Information

Gene Name BRD4
HF Protein Name Bromodomain-containing protein 4
HF Function Brd4 contributes to viral episome maintenance
Uniprot ID O60885
Protein Sequence View Fasta Sequence
NCBI Gene ID 23476
Host Factor (HF) Name in Paper Brd4
Gene synonyms HUNK1
Ensemble Gene ID ENSG00000141867
Ensemble Transcript ENST00000263377 [O60885-1];ENST00000360016 [O60885-3];ENST00000371835 [O60885-2]
KEGG ID Go to KEGG Database
Gene Ontology ID(s) GO:0000083, GO:0000794, GO:0000993, GO:0002039, GO:0003682, GO:0005634, GO:0005654, GO:0005694, GO:0005829, GO:0006325, GO:0006338, GO:0006351, GO:0006974, GO:0010971, GO:0016032, GO:0032968, GO:0043123, GO:0045944, GO:0050727, GO:0070577, GO:1901407, GO:2000002,
MINT ID O60885
STRING Click to see interaction map
GWAS Analysis Click to see gwas analysis
OMIM ID 608749
PANTHER ID N.A.
PDB ID(s) 2I8N, 2LSP, 2MJV, 2N3K, 2NCZ, 2ND0, 2ND1, 2NNU, 2OSS, 2OUO, 2YEL, 2YEM, 3MXF, 3P5O, 3SVF, 3SVG, 3U5J, 3U5K, 3U5L, 3UVW, 3UVX, 3UVY, 3UW9, 3ZYU, 4A9L, 4BJX, 4BW1, 4BW2, 4BW3, 4BW4, 4C66, 4C67, 4CFK, 4CFL, 4CL9, 4CLB, 4DON, 4E96, 4F3I, 4GPJ, 4HBV, 4HBW, 4HBX, 4HBY, 4HXK, 4HXL, 4HXM, 4HXN, 4HXO, 4HXP, 4HXR, 4HXS, 4IOO, 4IOQ, 4IOR, 4J0R, 4J0S, 4J3I, 4KV1, 4KV4, 4LR6, 4LRG, 4LYI, 4LYS, 4LYW, 4LZR, 4LZS, 4MEN, 4MEO, 4MEP, 4MEQ, 4MR3, 4MR4, 4NQM, 4NR8, 4NUC, 4NUD, 4NUE, 4O70, 4O71, 4O72, 4O74, 4O75, 4O76, 4O77, 4O78, 4O7A, 4O7B, 4O7C, 4O7E, 4O7F, 4OGI, 4OGJ, 4PCE, 4PCI, 4PS5, 4QB3, 4QR3, 4QR4, 4QR5, 4QZS, 4UIX, 4UIY, 4UIZ, 4UYD, 4WHW, 4WIV, 4X2I, 4XY9, 4XYA, 4YH3, 4YH4, 4Z1Q, 4Z1S, 4Z93, 4ZC9, 4ZW1, 5A5S, 5A85, 5ACY, 5AD2, 5AD3, 5BT4, 5CFW, 5COI, 5CP5, 5CPE, 5CQT, 5CRM, 5CRZ, 5CS8, 5CTL, 5CY9, 5D0C, 5D24, 5D25, 5D26, 5D3H, 5D3J, 5D3L, 5D3N, 5D3P, 5D3R, 5D3S, 5D3T, 5DLX, 5DLZ, 5DW2, 5DX4, 5E0R, 5EGU, 5EI4, 5EIS, 5F5Z, 5F60, 5F61, 5F62, 5F63, 5FBX, 5H21, 5HCL, 5HLS, 5HM0, 5HQ5, 5HQ6, 5HQ7, 5I80, 5I88, 5IGK, 5JWM, 5KDH, 5KHM, 5KJ0, 5KU3, 5LJ1, 5LJ2, 5LRQ, 5LUU, 5M39, 5M3A, 5MKZ, 5MLI, 5N2M, 5T35, 5TI2, 5TI3, 5TI4, 5TI5, 5TI6, 5TI7, 5U28, 5U2C, 5U2E, 5U2F, 5UEO, 5UEP, 5UEQ, 5UER, 5UES, 5UET, ,
pfam ID PF17035, PF17105, PF00439,
Drug Bank ID N.A.,
ChEMBL ID CHEMBL1163125
Organism Homo sapiens (Human)

Pathogen Information

Virus Name Human papillomavirus type 16
Virus Short Name HPV16
Order Unassigned
Virus Family Papillomaviridae
Virus Subfamily N.A.
Genus Alphapapillomavirus
Species Human papillomavirus 16
Host Human, monkeys
Cell Tropism Epithelial cells of skin, mucous membranes
Associated Disease Malignant tumours
Mode of Transmission Sexual, indirect and direct contact, auto-inoculation
VIPR DB link N.A.
ICTV DB link https://talk.ictvonline.org/ictv-reports/ictv_9th_report/dsdna-viruses-2011/w/dsdna_viruses/121/papillomaviridae
Virus Host DB link http://www.genome.jp/virushostdb/view/?virus_lineage=Papillomaviridae

Publication Information

Paper Title Abrogation of the Brd4-positive transcription elongation factor B complex by papillomavirus E2protein contributes to viral oncogene repression
Author's Name Junpeng Yan, Qing Li, Sam Lievens, Jan Tavernier and Jianxin You
Journal Name Journal Of Virology
Pubmed ID 19846528
Abstract The cellular bromodomain protein Brd4 is a major interacting partner of the papillomavirus (PV) E2 protein. Interaction of E2 with Brd4 contributes to viral episome maintenance. The E2-Brd4 interaction also plays an important role in repressing viral oncogene expression from the integrated viral genome in human PV (HPV)-positive cancer cells. However, the underlying mechanism is not clearly understood. In host cells, Brd4 recruits positive transcription elongation factor b (P-TEFb) to stimulate RNA polymerase II phosphorylation during cellular and viral gene expression. P-TEFb associates with the C terminus of Brd4, which largely overlaps with the E2 binding site on Brd4. In this study, we demonstrate that E2 binding to Brd4 inhibits the interaction of endogenous Brd4 and P-TEFb. P-TEFb is essential for viral oncogene E6/E7 transcription in both HeLa and CaSki cells that contain integrated HPV genomes. E2 binding to Brd4 abrogates the recruitment of P-TEFb to the integrated viral chromatin template, leading to inactivation of P-TEFb and repression of the viral oncogene E6/E7. Furthermore, dissociation of the Brd4-P-TEFb complex from the integrated viral chromatin template using a Brd4 bromodomain dominant-negative inhibitor also hampers HPV E6/E7 oncogene expression. Our data support that Brd4 recruitment of P-TEFb to the viral chromatin template is essential for viral oncogene expression. Abrogation of the interaction between P-TEFb and Brd4 thus provides a mechanism for E2-mediated repression of the viral oncogenes from the integrated viral genomes in cancer cells.
Used Model C33A, HEK293T, and HeLa cells
DOI 10.1128/JVI.01647-09