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Induction of proteasome-mediated degradation of CTIP2 by HIV-1 Vpr in microglial cells

Abstract : Usurping the host ubiquitination proteasome system (UPS) to inactivate the undesirable host protein is a common viral strategy. HIV-1 proteins inactivate the detrimental host proteins by this system. In Microglial cells, CTIP2 represses both initial phase and late phase of HIV-1 gene transcription. As HIV-1 can still replicate in the presence of CTIP2, we postulated that it might inactivate CTIP2 by using Cul4 E3 ubiquitin ligase complex to resume its replication. We observed higher CTIP2 expressions in the absence of Vpr, with no effect on CTIP2 mRNA and proteasome inhibitor can block this degradation. Co-immunoprecipitation assays showed that CTIP2 is associated with DCAF1 and DDB1 in the absence and presence of Vpr. We showed that this degradation is prevented by the using Vpr mutant (Q65R) and by knock down of DCAF1. Finally, we observed the co-localization of CTIP2 with Cul4A-DCAF1-DDB1 complex even in the absence of Vpr, in microglial cells. Additionally, DCAF1 interacts with CTIP2-associated heterochromatin enzymes complex. Our results suggest that Vpr expression increases the turnover of CTIP2 in HIV-1 productively infected cells. By degrading CTIP2, HIV-1 counteracts CTIP2-mediated silencing of its expression and favors its replication.
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https://tel.archives-ouvertes.fr/tel-00923199
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Submitted on : Thursday, January 2, 2014 - 2:26:21 AM
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  • HAL Id : tel-00923199, version 1

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Sultan Ali. Induction of proteasome-mediated degradation of CTIP2 by HIV-1 Vpr in microglial cells. Agricultural sciences. Université de Strasbourg, 2013. English. ⟨NNT : 2013STRAJ016⟩. ⟨tel-00923199⟩

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