Table 1.
EBNA-3 interacting cellular partners.
| Interacting proteins | Deregulated function | References |
|---|---|---|
| EBNA-3A | ||
| RBP-Jk | Recruits RBP-Jκ activity to regulate both viral and cellular gene transcription | Robertson et al., 1996; Maruo et al., 2005; Calderwood et al., 2011 |
| CtBP | Recruits CtBP to regulate gene transcription, for example p16INK4A | Hickabottom et al., 2002; Skalska et al., 2010 |
| Chk2 | Releases G2/M cell-cycle block | Krauer K. G. et al., 2004b |
| WDR48, WDR20, and USP46/UP12 | Forms a deubquitylation complex consisting of WDR48, WDR20, and USP46/USP12), possibly required to maintain LCL outgrowth | Ohashi et al., 2015 |
| MIZ-1 | Blocks the interaction between MIZ-1 and nucleophosmin and overall inhibits p15INK4B expression | Bazot et al., 2014 |
| 20S proteasome | Not yet described | Touitou et al., 2005 |
| Chaperones | Induces all of the factors necessary for an active Hsp70 chaperone complex including Hsp70, Hsp70B/B′, Bag3, and DNAJA1/Hsp40 | Young et al., 2008 |
| XAP-2 | Increased nuclear localization; however, precise function has not yet been described | Kashuba et al., 2000 |
| TCP-1 | Not yet described | Kashuba et al., 1999 |
| AhR | Enhances ligand dependent transactivation | Kashuba et al., 2006 |
| UK/UPRT | Increased nuclear localization; however, precise function has not yet been described | Kashuba et al., 2002 |
| EBNA-3B | ||
| RBP-Jκ | Recruits RBP-Jκ activity to regulate both viral and cellular gene transcription | Robertson et al., 1996 |
| Cyclin A | Not yet described | Knight and Robertson, 2004 |
| WDR48, WDR20, and USP46/UP12 | Forms a deubquitylation complex consisting of WDR48, WDR20, and USP46/USP12) | Ohashi et al., 2015 |
| 20S proteasome | Not yet described | Touitou et al., 2005 |
| EBNA-3C | ||
| RBP-Jκ | Recruits RBP-Jκ activity to regulate both viral and cellular gene transcription | Robertson et al., 1996; Lee et al., 2009; Calderwood et al., 2011; Kalchschmidt et al., 2016 |
| CtBP | Recruits CtBP to regulate gene transcription, for example p16INK4A | Touitou et al., 2001; Lee et al., 2009 |
| Prothymosin-α | Recruits prothymosin-α along with p300 to regulate gene transcription | Cotter and Robertson, 2000 |
| p300 | Recruits p300 activity to regulate cellular gene transcription | Subramanian et al., 2002a |
| Gemin3/DDX20 | Stabilizes and promotes a complex formation with p53 and thereby negatively affecting p53 transcriptional activity | Cai et al., 2011 |
| HDAC1 and HDAC2 | Recruits HDAC1/2 activity to regulate cellular gene transcription | Radkov et al., 1999; Knight et al., 2003 |
| mSin3A and NCoR | Functions in a complex with mSin3A and NCoR and represses transcription, for example p16INK4A | Knight et al., 2003; Jiang et al., 2014 |
| Spi1/PU1 | Recruits to regulate both viral and cellular gene transcription | Zhao and Sample, 2000 |
| Nm23-H1 | Modulates intrinsic transcriptional and anti-metastatic activities | Subramanian et al., 2001 |
| 20S proteasome | Not yet described | Touitou et al., 2005 |
| Cyclin A | Enhances Cyclin A/CDK2 kiase activity | Knight and Robertson, 2004; Knight et al., 2004 |
| Cyclin E | Not yet described | Knight et al., 2004 |
| Cyclin D1 | Enhances the kinase activity of Cyclin D1/CDK6 which enables subsequent ubiquitination and degradation of pRb | Knight et al., 2004; Saha et al., 2011b |
| GSK3β | Increases Cyclin D1 nuclear localization by blocking GSK3β activity | Saha et al., 2011b |
| p53 | Blocks p53 mediated transcriptional and apoptotic activities | Saha et al., 2009, 2011a; Yi et al., 2009 |
| Mdm2 | Enhances the intrinsic ubiquitin ligase activity of Mdm2 toward p53 | Saha et al., 2009 |
| ING4 and ING5 | Suppresses both ING4 and ING5 assisted p53 transcriptional activity | Saha et al., 2011a |
| E2F1 | Represses E2F1 transcriptional activity in response to DNA damage signals | Saha et al., 2012 |
| pRb | Facilitates pRb degradation in an ubiquitin-proteasome manner | Knight et al., 2005a |
| Chk2 | Releases the G2/M checkpoint block of cell-cycle | Choudhuri et al., 2007; Nikitin et al., 2010 |
| Gadd34 | Activates the upstream component of the UPR (eIF2α-phosphorylation) and blocks downstream UPR events (XBP1 activation and ATF6 cleavage) | Garrido et al., 2009 |
| SCFSkp2 | Recruits of SCFSkp2 E3 ligase activity to facilitate degradation of p27KIP1 and pRb | Knight et al., 2005a,b |
| c-Myc | Stabilizes and enhances transcription | Bajaj et al., 2008 |
| Sumo1/3 | Recruits SUMO-1/3 for EBNA-2 mediated transctivation | Rosendorff et al., 2004 |
| MRPS18-2 | Releases E2F1 and thereby facilitates G1-S transition of the cell-cycle | Kashuba et al., 2008 |
| Aurora kinase B | Negatively regulates p53 and pRb activities through stabilizing Aurora kinase B activity | Jha et al., 2013, 2015 |
| IRF4/8 | Stabilizes IRF4 and dowregulates IRF8; Recruits for modulating cellular gene transcription | Banerjee et al., 2013; Jiang et al., 2014 |
| H2AX | Destabilizes H2AX and restricts H2AX expression into nucleus | Nikitin et al., 2010; Jha et al., 2014 |
| USP46/USP12 | Recruits USP46/USP12 dubiquitination activity to regulate p14ARF transcription | Ohashi et al., 2015 |
| p73 | Blocks p73 mediated apoptosis | Sahu et al., 2014 |