NUCKS1, a novel Tat coactivator, plays a crucial role in HIV-1 replication by increasing Tat-mediated viral transcription on the HIV-1 LTR promoter

Kim, Hye-Young; Choi, Byeong‐Sun; Kim, Sung Hoon; Roh, Tae-Young; Park, Jihwan; Yoon, Choon Sik

doi:10.1186/preaccept-1444760432121123

Cited by 7 publications

(7 citation statements)

References 43 publications

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“…Western blot analysis was performed as previously described [ 22 ]. Briefly, cells were treated with an anticancer drug, 5-FU, doxorubicin, or etoposide for 12 h and then harvested in RIPA buffer (Cell Signaling Technology) containing a complete EDTA-free protease and phosphatase inhibitor cocktail (Roche).…”

Section: Methodsmentioning

confidence: 99%

“…5 (HSS186391): CCG CCU GAG GUU GGC UCU GAC UGU A. Knockdown of p53 was performed by electroporation as described previously [ 12 ]. Briefly, 1 × 10 7 cells were electroporated with 500 pmole of control siRNA (si-con; Invitrogen) or p53 siRNAs in 0.4 cm cuvettes at 960 μF and 250 V. The ectopic expression of p53 in J1.1 cells was performed by electroporation using a Nucleofector™ kit X (Lonza) with 5 μg of pcDNA3- Flag-tagged p53 according to the manufacturer’s protocol [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

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Highly activated p53 contributes to selectively increased apoptosis of latently HIV-1 infected cells upon treatment of anticancer drugs

Shin

Lim

Choi

et al. 2016

Virol J

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BackgroundDespite the successful inhibition of human immunodeficiency virus type 1 (HIV-1) replication by combination antiretroviral therapy, cells latently infected with HIV-1 remaining in patients are a major obstacle for eradication of HIV-1 infection. The tumor suppressor factor p53 is activated by HIV-1 infection, and restricts HIV-1 replication. However, a therapeutic strategy based on p53 activity has not been considered for elimination of latently infected cells.MethodsApoptotic cells were analyzed using flow cytometry with anti-annexin A5-FITC Ab and PI staining upon treatment of anticancer drugs. The expression and activation of p53 and apoptotic molecules in latently HIV-1-infected T cells were compared using Western blot analysis. The role of p53 in the anticancer drug treatment-induced apoptosis of cells latently infected with HIV-1 was determined by knock-down experiment using siRNA against p53.ResultsUpon treatment with 5-fluorouracil (5-FU), apoptosis was increased in latently infected ACH2 cells encoding competent p53 compared with uninfected parent A3.01 cells, while the apoptosis of latently infected p53 null J1.1 cells was less than that of uninfected cells. Treatment with 5-FU increased the levels of cleaved caspase-3 and PARP in ACH2 cells compared with uninfected and latently infected p53 null J1.1 cells. The levels of expression and activation of p53 were higher in both latently infected ACH2 and NCHA2 cells than in uninfected cells. Furthermore, the activation levels of p53 in both cells were further increased upon 5-FU treatment. Consistent with p53 status, apoptosis was markedly increased in ACH2 and NCHA2 cells compared with uninfected and latently infected J1.1 cells upon treatment with other anticancer drugs such as doxorubicin and etoposide. Inhibition of p53 in cells with latent HIV-1 infection diminished apoptosis upon 5-FU treatment.ConclusionEvidence described here indicate that when treated with anticancer drugs, apoptosis of cells with latent HIV-1 infection was increased via the p53 activation pathway and may provide information for application of anticancer drugs to selectively eliminate HIV-1 reservoirs.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Highly activated p53 contributes to selectively increased apoptosis of latently HIV-1 infected cells upon treatment of anticancer drugs

Shin

Lim

Choi

et al. 2016

Virol J

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“…Low levels of NUCKS1 in latently infected cell line models such as ACH2 and J1.1 as compared to the parental cell lines, may explain HIV entry into latency [143]. NUCKS1 binds directly to Tat and seems important for the recruitment of Tat to TAR, since its depletion decreases Tat interaction with TAR.…”

Section: Host Factors Influencing Hiv-1 Latencymentioning

confidence: 99%

Role of Host Factors on the Regulation of Tat-Mediated HIV-1 Transcription

Mousseau

Valente

2017

CPD

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Background The viral transactivator Tat protein is a key modulator of HIV-1 replication, as it regulates transcriptional elongation from the integrated proviral genome. Tat recruits the human transcription elongation factor b, and other host proteins, such as the super elongation complex, to activate the cellular RNA polymerase II, normally stalled shortly after transcription initiation at the HIV promoter. By means of a complex set of interactions with host cellular factors, Tat determines the fate of viral activity within the infected cell. The virus will either actively replicate to promote dissemination in blood and tissues, or become dormant mostly in memory CD4+ T cells, as part of a small but long-living latent reservoir, the main obstacle for HIV eradication. Objective In this review, we summarize recent advances in the understanding of the multi-step mechanism that regulates Tat-mediated HIV-1 transcription and RNA polymerase II release, to promote viral transcription elongation. Early events of the human transcription elongation factor b release from the inhibitory 7SK small nuclear ribonucleoprotein complex and its recruitment to the HIV promoter will be discussed. Specific roles of the super elongation complex subunits during transcription elongation, and insight on recently identified cellular factors and mechanisms regulating HIV latency will be detailed. Conclusion Understanding the complexity of HIV transcriptional regulation by host factors may open the door for development of novel strategies to eradicate the resilient latent reservoir.

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“…It is therefore posited that Tat is able to promote viral replication at the very early stage of HIV-1 transcription before TAR is formed [ 14 ]. Multiple host cellular factors such as Sp1, nuclear factor κB (NF-κB), TATA-binding protein (TBP), nuclear factor of activated T cells (NFAT), are essential for the TAR-independent transcriptional activity of Tat [ 7 , 9 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Cellular RelB interacts with the transactivator Tat and enhance HIV-1 expression

et al. 2018

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BackgroundHuman immunodeficiency virus type 1 (HIV-1) Tat protein plays an essential role in HIV-1 gene transcription. Tat transactivates HIV-1 long terminal repeat (LTR)-directed gene expression through direct interactions with the transactivation-responsive region (TAR) element and other cis elements in the LTR. The TAR-independent Tat-mediated LTR transactivation is modulated by several host factors, but the mechanism is not fully understood.ResultsHere, we report that Tat interacts with the Rel homology domain of RelB through its core region. Furthermore, RelB significantly increases Tat-mediated transcription of the HIV-1 LTR and viral gene expression, which is independent of the TAR. Both Tat and RelB are recruited to the HIV-1 promoter, of which RelB facilitates the recruitment of Tat to the viral LTR. The NF-κB elements are key to the accumulation of Tat and RelB on the LTR. Knockout of RelB reduces the accumulation of RNA polymerase II on the LTR, and decreases HIV-1 gene transcription. Together, our data suggest that RelB contributes to HIV-1 transactivation.ConclusionsOur results demonstrate that RelB interacts with Tat and enhances TAR-independent activation of HIV-1 LTR promoter, which adds new insights into the multi-layered mechanisms of Tat in regulating the gene expression of HIV-1.Electronic supplementary materialThe online version of this article (10.1186/s12977-018-0447-9) contains supplementary material, which is available to authorized users.

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NUCKS1, a novel Tat coactivator, plays a crucial role in HIV-1 replication by increasing Tat-mediated viral transcription on the HIV-1 LTR promoter

Cited by 7 publications

References 43 publications

Highly activated p53 contributes to selectively increased apoptosis of latently HIV-1 infected cells upon treatment of anticancer drugs

Highly activated p53 contributes to selectively increased apoptosis of latently HIV-1 infected cells upon treatment of anticancer drugs

Role of Host Factors on the Regulation of Tat-Mediated HIV-1 Transcription

Cellular RelB interacts with the transactivator Tat and enhance HIV-1 expression

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