Move or Die: the Fate of the Tax Oncoprotein of HTLV-1
Abstract
:1. Introduction
2. Tax Intracellular Distribution and Functional Structure
3. Tax Posttranslational Modifications
3.1. Ubiquitination of Tax
3.2. Sumoylation of Tax
3.3. Proline Isomerization of Tax
3.4. Acetylation of Tax
3.5. Phosphorylation of Tax
4. Distribution of Tax in the Nucleus
4.1. Structure of the Tax Nuclear Bodies
4.2. Composition of Tax Nuclear Bodies
4.3. Morphogenesis of the Tax Nuclear Bodies
4.4. Function of the Tax Nuclear Bodies
5. Distribution of Tax in the Cytoplasm
6. Migration of Tax in and out of the Nucleus
7. Tax Intracellular Trafficking and Activation of the NF-κB Pathway
8. Conclusions
- Is SUMO/SIM interaction the basis for recruitment of Tax partners to the Tax NBs?
- Do the HTLV-1 provirus and specific cellular genes contact the surface of the Tax NBs in the course of viral and cellular transcription?
- What is the role of IKKγ/NEMO in the Tax NBs?
- How does the crosstalk between Tax NBs and PML NBs impact on prevention of apoptosis by Tax?
- Does calreticulin participate in Tax and IKKγ/NEMO export from the nucleus?
- How does proline isomerization by Pin1 and polyubiquitination by PDLIM2 affect Tax transcriptional and transforming activities?
- Which specific events occur in the cytoplasmic foci that contain Tax, TAB2, TAX1-BP1, IKKγ/NEMO and calreticulin?
- How does assembly of Tax/IKK complexes in the Golgi-associated structures lead to IKK activation?
- Is Tax accumulation in the Golgi involved in its transport to the nucleus?
- Must Tax be demodified in the process of nuclear entry?
- Which kinases phosphorylate Tax in the cytoplasm and in the nucleus?
- A question of central importance is whether Tax-induced genotoxic stress creates a signal in the nucleus that triggers activation of the NF-κB pathway.
Acknowledgements
References and Notes
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Function/comment | Methods* | References | |
Components detected in the Tax NBs | |||
Transcription | |||
Tax | HTLV-1 oncoprotein | LM/EM | [33,34] |
Pol IIO | Hyperphosphorylated form of RNA polymerase II | LM | [34,70] |
RelA | NF-κB subunit | LM/coIP | [32,34,65,81,83] |
p50 | NF-κB subunit | LM/coIP | [34,84] |
IKKγ/NEMO | Regulatory subunit of IκB kinase/NF-κB Essential | LM/coIP | [23,27,32 |
modulator | 43,81,82,85,86,87] | ||
ATF1 | Activating Transcription Factor 1, member of CREB/ATF | LM | [13] |
transcription factor family | |||
CBP and p300 | Homologous transcriptional coactivators, acetyltransferases | LM/coIP | [10,13,65,88,89] |
SMRT | Silencing mediator for retinoic acid and thyroid hormone | LM | [74] |
receptors | |||
Splicing | |||
Sm | Core components of snRNP | LM/EM | [34,90] |
SC-35 | Member of SR protein family | LM/coIP | [33,34] |
DNA damage | |||
response | |||
DNA-PKcs | DNA-dependent protein kinase catalytic subunit | LM | [91] |
BRCA1 | Breast cancer 2 | LM | [91] |
MDC1 | Mediator of DNA damage checkpoint protein 1 | LM | [91] |
ChK2 | Checkpoint kinase 2 | LM | [92] |
53BP1 | p53 binding protein 1 | LM | [93] |
Protein modification | |||
CBP and p300 | Homologous transcriptional coactivators, acetyltransferases | LM/coIP | [10,13,65,88,89], |
Figure 6 | |||
Ubc9 | SUMO E2 conjugating enzyme | LM | [82] |
ChK2 | Checkpoint kinase 2 | LM | [93] |
CDK8 | Cyclin-dependent kinase 8 | LM | [34] |
SUMO-1 | Small ubiquitin-like modifier | LM | [32,51] |
Nucleocytoplasmic | |||
transport | |||
CRM-1 | Chromosome region maintenance protein 1, nuclear export | LM | [70] |
Calreticulin | Calcium-buffering chaperone, nuclear export of hormone | LM | [81] |
receptors | |||
Nucleotides | |||
Nascent RNA | Nascent ribonucleic acid | LM | [70] |
Components not detected in Tax NBs | |||
PML | Promyelocytic leukemia protein: component of PML NBs | LM | [32,34,74], |
Figure 3A, Figure 4, Figure 6 | |||
Coilin | Component of Cajal bodies | LM | [34,90] |
Nbs1 | Component of the repair foci | LM | [91] |
Ubiquitin (Ub) | 76 amino acid peptide conjugated to lysines of target proteins, | LM | [32] |
either as mono-Ub or via branching at lysine K48 or K63 of Ub | |||
p53 | Tumor suppressor p53 | LM | Figure 6 |
DNA | Desoxyribonucleic acid | LM/EM | [70,90] |
Rex | HTLV-1 post-transcriptional regulator | LM | [70] |
Function/comment | Methods* | References | |
Golgi-associated lipid | |||
raft microdomains | |||
Tax | HTLV-1 oncoprotein | LM | [32,54,120,121] |
IKKγ/ΝΕΜO | Regulatory subunit of IκB kinase/NF-κB Essential Modulator | LM/LRF | [32,54,121] |
IKKα | Catalytic subunit α of IKK | LM/LRF | [54,121] |
IKKβ | Catalytic subunit β of IKK | LM/LRF | [54,121] |
Hsp90 | Heat shock protein 90, IKK-associated chaperone protein | LRF | [54] |
TAK1 | TGFβ activating kinase, IKK-upstream kinase | LRF | [54] |
GM130 | Golgi matrix protein 130, marker of the Golgi apparatus | LM | [54,120,121] |
Giantin | Marker of the Golgi apparatus | LM | [120] |
GM1, LAT, Calveolin | Markers of lipid rafts | LM/LRF | [54] |
Ubiquitin (Ub) | 76 amino acid peptide conjugated to lysines of target proteins, | LM | [32] |
either as mono-Ub or via branching at lysines K48 or K63 | |||
of Ub | |||
TAB2-containing | |||
cytoplasmic foci | |||
Tax | HTLV-1 oncoprotein | LM | [81] |
RelA | NF-κB subunit | LM/coIP | [81] |
Calreticulin | Calcium-buffering chaperone, nuclear export of hormone | LM/coIP | [81,122] |
receptors | |||
IKKγ/ΝΕΜO | Regulatory subunit of IκB kinase/NF-κB Essential Modulator | LM/coIP | [32,81] |
IKKα | Catalytic subunit α of IKK | LM | [32] |
IKKβ | Catalytic subunit β of IKK | LM | [32] |
TAB2 | TGFβ activating kinase binding protein 2 | LM | [81] |
TAX1-BP1 | TAX1 binding protein 1, component of the | LM | [81] |
A20/Itch/TAX1-BP1 ubiquitin editing complexes | |||
Centrosome | |||
Tax | HTLV-1 oncoprotein | LM/coIP | [59] |
γ-Tubulin | Marker of the centrosome | LM/coIP | [59] |
IKKγ/ΝΕΜO | Regulatory subunit of IκB kinase/NF-κB Essential Modulator | LM/coIP | [59] |
IKKα | Catalytic subunit α of IKK | coIP | [59] |
IKKβ | Catalytic subunit β of IKK | coIP | [59] |
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Lodewick, J.; Lamsoul, I.; Bex, F. Move or Die: the Fate of the Tax Oncoprotein of HTLV-1. Viruses 2011, 3, 829-857. https://doi.org/10.3390/v3060829
Lodewick J, Lamsoul I, Bex F. Move or Die: the Fate of the Tax Oncoprotein of HTLV-1. Viruses. 2011; 3(6):829-857. https://doi.org/10.3390/v3060829
Chicago/Turabian StyleLodewick, Julie, Isabelle Lamsoul, and Françoise Bex. 2011. "Move or Die: the Fate of the Tax Oncoprotein of HTLV-1" Viruses 3, no. 6: 829-857. https://doi.org/10.3390/v3060829
APA StyleLodewick, J., Lamsoul, I., & Bex, F. (2011). Move or Die: the Fate of the Tax Oncoprotein of HTLV-1. Viruses, 3(6), 829-857. https://doi.org/10.3390/v3060829