Table 1.
A comparison of the activities and functional consequences of Tax and HTLV-1 basic zipper protein (HBZ).
| Tax Activities | Functional Consequences | HBZ Activities | Functional Consequences |
|---|---|---|---|
| CREB, CBP/p300, P/CAF, TORC interaction | Activate viral transcription | CREB, CBP/p300 interaction | Suppress viral gene expression |
| Association with MTOC | Promote formation of virological synapse and cell–cell transmission | Rex inhibition | Suppress viral gene expression and particle production |
| RNF8, UBC13 interaction and activation | Stimulate K63-linked polyubiquitin chain assembly | NF-κB DNA-binding disruption and p65/RelA degradation | Suppress Tax-mediated canonical NF-κB activation |
| TAK1, IKK, MKK, JNK, mTOR, etc. activation | Activate c-Jun/AP and SRF | Prevent senescence induction | |
| Canonical NF-κB activation | Induce expression of cytokines, cytokine receptors, adhesion molecules, anti-apoptotic factors, etc. | Promote viral latency and persistence of virus-infected cells | |
| p21WAF1 and p27KIP1 up-regulation | Induce senescence | ||
| NIK, p100 interaction Non-canonical NF-κB activation |
Induce expression of cytokines, cytokine receptors, adhesion molecules, anti-apoptotic factors, etc. | E2F1 activation | Promote cell proliferation and apoptosis |
| Survivin up-regulation (HBZ RNA) | Prevent apoptosis | ||
| CDK 2/4 activation E2F1 activation |
Promote cell cycle progression | Onco-miRs activation | Promote cell proliferation |
| Cyclin D1 activation P53, Rb, DLG1 inactivation |
hTERT activation BDNF/TrkB activation |
||
| PCNA activation | Wnt5a, JunD activation | ||
| CENP-B repression | |||
| hTERT activation | Promote cell immortalization | Foxp3 induction and functional inactivation | Modify T-cells |
| P53 inactivation Sequestration of DDR mediator MDC1 Inactivation of DDR mediators CHK1 and CHK2 Suppression of DNA Polβ expression |
Induce genomic instability | Bim repression via Foxo3a IFNγ repression Activation of mTOR/suppression of autophagy |
Promote cell survival during stress response |
| Activation of APC/C | Promote aneurploidy, cytokinesis defect, and senescence | TIGIT induction | Impair antiviral immunity and promote immune evasion |
| RANBP1, TaxBP2 (Rootletin isoform 2) interaction | Promote centrosome amplification or fragmentation |
CREB: cAMP response element-binding protein; CBP/p300: Tax-CREB binding protein (CBP)/p300; P/CAF: p300/CBP-associated factor; TORC: transducers of regulated CREB; MTOC: microtubule organizing centers; RNF8: ring finger protein 8; UBC13: ubiquitin E2 conjugating enzyme; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B-cells; TAK1: TGFβ)-activated kinase 1; IKK: I kappa B kinase; MKK: mitogen-activated protein kinase kinase; JNK: c-Jun N-terminal kinase; mTOR: mammalian target of rapamycin; AP: activator protein; SRF: serum response factor; NIK: NF-κB-inducing kinase; E2F1: E2F transcription factor 1; CDK: cyclin-dependent kinase; Rb: retinoblastoma protein; DLG1: disks large homolog 1; hTERT: human telomerase reverse transcriptase; BDNF: brain-derived neurotrophic factor; TrkB: tropomyosin receptor kinase B; PCNA: proliferating cell nuclear antigen; Wnt5a: Wingless-Type MMTV Integration Site Family, Member 5A; CENP-B: centromere protein B; FOXP3: forkhead box P3; BIM: Bcl2-interacting mediator of cell death; FOXO3a: forkhead box O3a; DDR: DNA damage repair; MDC1: mediator of DNA damage checkpoint protein 1; IFNγ: interferon gamma; CHK1: checkpoint kinase 1; CHK2: checkpoint kinase 2; APC/C: anaphase-promoting complex/cyclosome; TIGIT: T-cell receptor with immunoglobulin and ITIM domains; RANBP1: Ran-specific binding protein 1.