TY  - JOUR
A1  - Maudet, Claire
A1  - Sourisce, Adèle
A1  - Dragin, Loïc
A1  - Lahouassa, Hichem
A1  - Rain, Jean-Christopher
A1  - Bouaziz, Serge
A1  - Ramirez, Bertha Cécilia
A1  - Margottin-Goguet, Florence
T1  - HIV-1 Vpr Induces the Degradation of ZIP and sZIP, Adaptors of the NuRD Chromatin Remodeling Complex, by Hijacking DCAF1/VprBP
JF  - PLOS ONE
N2  - The Vpr protein from type 1 and type 2 Human Immunodeficiency Viruses (HIV-1 and HIV-2) is thought to inactivate several host proteins through the hijacking of the DCAF1 adaptor of the Cul4A ubiquitin ligase. Here, we identified two transcriptional regulators, ZIP and sZIP, as Vpr-binding proteins degraded in the presence of Vpr. ZIP and sZIP have been shown to act through the recruitment of the NuRD chromatin remodeling complex. Strikingly, chromatin is the only cellular fraction where Vpr is present together with Cul4A ubiquitin ligase subunits. Components of the NuRD complex and exogenous ZIP and sZIP were also associated with this fraction. Several lines of evidence indicate that Vpr induces ZIP and sZIP degradation by hijacking DCAF1: (i) Vpr induced a drastic decrease of exogenously expressed ZIP and sZIP in a dose-dependent manner, (ii) this decrease relied on the proteasome activity, (iii) ZIP or sZIP degradation was impaired in the presence of a DCAF1-binding deficient Vpr mutant or when DCAF1 expression was silenced. Vpr-mediated ZIP and sZIP degradation did not correlate with the growth-related Vpr activities, namely G2 arrest and G2 arrest-independent cytotoxicity. Nonetheless, infection with HIV-1 viruses expressing Vpr led to the degradation of the two proteins. Altogether our results highlight the existence of two host transcription factors inactivated by Vpr. The role of Vpr-mediated ZIP and sZIP degradation in the HIV-1 replication cycle remains to be deciphered.
KW  - immunodeficiency-virus type-1
KW  - MI-2/NURD complex
KW  - cell-cycle arrest
KW  - CUL4-DDB1 ubiquitin ligase
KW  - viral protein-R
KW  - NF-KAPPA-B
KW  - macrophage infection
KW  - enzyme APOBEC3G
KW  - in-vivo
KW  - transcription
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128316
SN  - 1932-6203
VL  - 8
IS  - 10
ER  - 
TY  - JOUR
A1  - Wolf, Annette
A1  - Akrap, Nina
A1  - Marg, Berenice
A1  - Galliardt, Helena
A1  - Heiligentag, Martyna
A1  - Humpert, Fabian
A1  - Sauer, Markus
A1  - Kaltschmidt, Barbara
A1  - Kaltschmidt, Christian
A1  - Seidel, Thorsten
T1  - Elements of Transcriptional Machinery Are Compatible among Plants and Mammals
JF  - PLoS ONE
N2  - In the present work, the objective has been to analyse the compatibility of plant and human transcriptional machinery. The experiments revealed that nuclear import and export are conserved among plants and mammals. Further it has been shown that transactivation of a human promoter occurs by human transcription factor NF-\(\kappa\) B in plant cells, demonstrating that the transcriptional machinery is highly conserved in both kingdoms. Functionality was also seen for regulatory elements of NF-\(\kappa\) B such as its inhibitor I\(\kappa\)B isoform \(\alpha\) that negatively regulated the transactivation activity of the p50/RelA heterodimer by interaction with NF-\(\kappa\)B in plant cells. Nuclear export of RelA could be demonstrated by FRAP-measurements so that RelA shows nucleo-cytoplasmic shuttling as reported for RelA in mammalian cells. The data reveals the high level of compatibility of human transcriptional elements with the plant transcriptional machinery. Thus, Arabidopsis thaliana mesophyll protoplasts might provide a new heterologous expression system for the investigation of the human NF-\(\kappa\)B signaling pathways. The system successfully enabled the controlled manipulation of NF-\(\kappa\)B activity. We suggest the plant protoplast system as a tool for reconstitution and analyses of mammalian pathways and for direct observation of responses to e. g. pharmaceuticals. The major advantage of the system is the absence of interference with endogenous factors that affect and crosstalk with the pathway.
KW  - complexes
KW  - in vivo
KW  - DNA-binding
KW  - nuclear proe
KW  - gene expression
KW  - NF-KAPPA-B
KW  - RNA-binding protein
KW  - alpha
KW  - inflammation
KW  - homodimers
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131203
VL  - 8
IS  - 1
ER  -