The interaction of the gammaherpesvirus 68 orf73 protein with cellular BET proteins affects the activation of cell cycle promoters.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Stewart, James P
Schulz, Thomas F
MetadataShow full item record
AbstractInfection of mice with murine gammaherpesvirus 68 (MHV-68) provides a valuable animal model for gamma-2 herpesvirus (rhadinovirus) infection and pathogenesis. The MHV-68 orf73 protein has been shown to be required for the establishment of viral latency in vivo. This study describes a novel transcriptional activation function of the MHV-68 orf73 protein and identifies the cellular bromodomain containing BET proteins Brd2/RING3, Brd3/ORFX, and BRD4 as interaction partners for the MHV-68 orf73 protein. BET protein members are known to interact with acetylated histones, and Brd2 and Brd4 have been implicated in fundamental cellular processes, including cell cycle regulation and transcriptional regulation. Using MHV-68 orf73 peptide array assays, we identified Brd2 and Brd4 interaction sites in the orf73 protein. Mutation of one binding site led to a loss of the interaction with Brd2/4 but not the retinoblastoma protein Rb, to impaired chromatin association, and to a decreased ability to activate the BET-responsive cyclin D1, D2, and E promoters. The results therefore pinpoint the binding site for Brd2/4 in a rhadinoviral orf73 protein and suggest that the recruitment of a member of the BET protein family allows the MHV-68 orf73 protein to activate the promoters of G(1)/S cyclins. These findings point to parallels between the transcriptional activator functions of rhadinoviral orf73 proteins and papillomavirus E2 proteins.
CitationThe interaction of the gammaherpesvirus 68 orf73 protein with cellular BET proteins affects the activation of cell cycle promoters. 2009, 83 (9):4423-34 J. Virol.
AffiliationHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
JournalJournal of virology
- A structural basis for BRD2/4-mediated host chromatin interaction and oligomer assembly of Kaposi sarcoma-associated herpesvirus and murine gammaherpesvirus LANA proteins.
- Authors: Hellert J, Weidner-Glunde M, Krausze J, Richter U, Adler H, Fedorov R, Pietrek M, Rückert J, Ritter C, Schulz TF, Lührs T
- Issue date: 2013
- Kaposi's sarcoma-associated herpesvirus LANA-1 interacts with the short variant of BRD4 and releases cells from a BRD4- and BRD2/RING3-induced G1 cell cycle arrest.
- Authors: Ottinger M, Christalla T, Nathan K, Brinkmann MM, Viejo-Borbolla A, Schulz TF
- Issue date: 2006 Nov
- Brd2/RING3 interacts with a chromatin-binding domain in the Kaposi's Sarcoma-associated herpesvirus latency-associated nuclear antigen 1 (LANA-1) that is required for multiple functions of LANA-1.
- Authors: Viejo-Borbolla A, Ottinger M, Brüning E, Bürger A, König R, Kati E, Sheldon JA, Schulz TF
- Issue date: 2005 Nov
- Solution structure of the second bromodomain of Brd2 and its specific interaction with acetylated histone tails.
- Authors: Huang H, Zhang J, Shen W, Wang X, Wu J, Wu J, Shi Y
- Issue date: 2007 Sep 12
- Bromodomain analysis of Brd2-dependent transcriptional activation of cyclin A.
- Authors: Sinha A, Faller DV, Denis GV
- Issue date: 2005 Apr 1