Cullin4A and Cullin4B Are Interchangeable for HIV Vpr and Vpx Action through the CRL4 Ubiquitin Ligase Complex

Sharifi, Hamayun J.; Furuya, Andrea; Jellinger, Robert M.; Nekorchuk, Michael; Noronha, Carlos M. C. de

doi:10.1128/jvi.00241-14

Cited by 12 publications

(8 citation statements)

References 108 publications

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“…Vpr binding protein (VprBP), which is also known as DDB1-Cul4A associated factor 1 (DCAF1), acts as an adaptor to link Vpr to the CUL ubiquitin E3 ligase system [41], [42]. Several proteins, including UNG2 and SMUG1, have been reported to be targets of Vpr through this proteasome system [27], [28].…”

Section: Resultsmentioning

confidence: 99%

The Human Antiviral Factor TRIM11 Is under the Regulation of HIV-1 Vpr

et al. 2014

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TRIM11 has been reported to be able to restrict HIV-1 replication, but the detailed aspects of the interfering mechanisms remain unclear. In this study, we demonstrated that TRIM11 mainly suppressed the early steps of HIV-1 transduction, resulting in decreased reverse transcripts. Additionally, we found that TRIM11 could inhibit HIV-1 long terminal repeat (LTR) activity, which may be related to its inhibitory effects on NF-κB. Deletion mutant experiments showed that the RING domain of TRIM11 was indispensable in inhibiting the early steps of HIV-1 transduction but was dispensable in decreasing NF-κB and LTR activities. Moreover, we found that low levels of Vpr decreased TRIM11 protein levels, while high levels increased them, and these regulations were independent of the VprBP-associated proteasome machinery. These results suggest that the antiviral factor TRIM11 is indirectly regulated by HIV-1 Vpr through unknown mechanisms and that the concentration of Vpr is essential to these processes. Thus, our work confirms TRIM11 as a host cellular factor that interferes with the early steps of HIV-1 replication and provides a connection between viral protein and host antiviral factors.

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Section: Resultsmentioning

confidence: 99%

The Human Antiviral Factor TRIM11 Is under the Regulation of HIV-1 Vpr

et al. 2014

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“…These results agrees with the findings by Bergamaschi et al and Allouch et al that p21 restricted HIV-2 and SIV infection [ 16 , 17 ]. Since Vpx proteins in HIV-2 and SIV are able to target SAMHD1 for proteasomal degradation [ 30 , 45 , 46 ], the p21 dependent block of HIV-2 in hMDMs suggested a mechanism of host restriction that is less dependent on the level of cellular dNTPs.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of HIV early replication by the p53 and its downstream gene p21

Shi

Sharifi

DiGrigoli

et al. 2018

Virol J

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BackgroundThe tumor suppressor gene p53 has been found to suppress HIV infection by various mechanisms, but the inhibition of HIV at an early stage of replication by host cell p53 and its downstream gene p21 has not been well studied.MethodVSV-G pseudotyped HIV-1 or HIV-2 viruses with GFP or luciferase reporter gene were used to infect HCT116 p53+/+ cells, HCT116 p53−/− cells and hMDMs. The infections were detected by flow cytometry or measured by luciferase assay. Reverse transcription products were quantified by a TaqMan real time PCR. siRNA knockdown experiments were applied to study potential roles of p53 and p21 genes in their restriction to HIV infection. Western blot experiments were used to analyze changes in gene expression.ResultsThe infection of HIV-1 was inhibited in HCT116 p53+/+ cells in comparison to HCT116 p53−/− cells. The fold of inhibition was largely increased when cell cycle switched from cycling to non-cycling status. Further analysis showed that both p53 and p21 expressions were upregulated in non-cycling HCT116 p53+/+ cells and HIV-1 reverse transcription was subsequently inhibited. siRNA knockdown of either p53 or p21 rescued HIV-1 reverse transcription from the inhibition in non-cycling HCT116 p53+/+ cells. It was identified that the observed restrictions by p53 and p21 were associated with the suppression of RNR2 expression and phosphorylation of SAMHD1. These observations were confirmed by using siRNA knockdown experiments. In addition, p53 also inhibited HIV-2 infection in HCT116 p53+/+ cells and siRNA knockdown of p21 increased HIV-2 infection in hMDMs. Finally the expressions of p53 and p21 were found to be induced in hMDMs shortly after HIV-1 infection.ConclusionsThe p53 and its downstream gene p21 interfere with HIV early stage of replication in non-cycling cells and hMDMs.

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“…Both UNG2 and SMUG1 function to prevent mutagenesis by eliminating uracil from DNA molecules via cleaving the N-glycosylic bond and initiating the BER pathway 41 , 42 . CRL4 ubiquitin ligase can mediate UNG2 and SMUG1 degradation, thereby maintaining genome integrity 43 , 44 .…”

Section: Cullins Dna Damage and Repairmentioning

confidence: 99%

Cullin Family Proteins and Tumorigenesis: Genetic Association and Molecular Mechanisms

Chen¹,

Sui²,

Zhang³

et al. 2015

J. Cancer

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Cullin family proteins function as scaffolds to form numerous E3 ubiquitin ligases with RING proteins, adaptor proteins and substrate recognition receptors. These E3 ligases further recognize numerous substrates to participate in a variety of cellular processes, such as DNA damage and repair, cell death and cell cycle progression. Clinically, cullin-associated E3 ligases have been identified to involve numerous human diseases, especially with regard to multiple cancer types. Over the past few years, our understanding of cullin proteins and their functions in genome stability and tumorigenesis has expanded enormously. Herein, this review briefly provides current perspectives on cullin protein functions, and mainly summarizes and discusses molecular mechanisms of cullin proteins in tumorigenesis.

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Cullin4A and Cullin4B Are Interchangeable for HIV Vpr and Vpx Action through the CRL4 Ubiquitin Ligase Complex

Cited by 12 publications

References 108 publications

The Human Antiviral Factor TRIM11 Is under the Regulation of HIV-1 Vpr

The Human Antiviral Factor TRIM11 Is under the Regulation of HIV-1 Vpr

Inhibition of HIV early replication by the p53 and its downstream gene p21

Cullin Family Proteins and Tumorigenesis: Genetic Association and Molecular Mechanisms

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