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| Status |
Public on Feb 06, 2013 |
| Title |
Host cell subversion by Toxoplasma GRA16, an exported dense granule protein that targets the host cell nucleus and alters gene expression |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
After invading host cells, Toxoplasma gondii multiplies within a parasitophorous vacuole (PV) that is maintained by parasite proteins secreted from organelles called dense granules. Most dense granule proteins remain within the PV and few are known to access the host cell cytosol. We identify GRA16 as a dense granule protein that is exported through the PV membrane and reaches the host cell nucleus where it positively modulates genes involved in cell cycle progression and the p53 tumor suppressor pathway. GRA16 binds two host enzymes, the deubiquitinase HAUSP and PP2A phosphatase, which exert several functions, including regulation of p53 and the cell cycle. GRA16 alters p53 levels in a HAUSP-dependent manner and induces nuclear translocation of the PP2A holoenzyme. Additionally, certain GRA16-deficient strains exhibit attenuated virulence, indicating the importance of these host alterations in pathogenesis. Therefore, GRA16 represents a potentially emerging subfamily of exported dense granule proteins that modulate host function.
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| Overall design |
Mouse bone marrow-derived macrophages (BMDM) or Human foreskin fibroblasts (HFFs) were infected with the following Toxoplasma gondii strains:
- RHku80 WT versus RHku80(deltaGRA16) mutant (in BMDM)
- Pruku80 WT versus Pruku80(deltaGRA16) mutant (in BMDM)
- RHku80 WT versus RHku80(deltaGRA16) mutant (in HFF)
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| Contributor(s) |
Bougdour A, Durandau E, Ortet P, Barakat M, Brenier-Pinchart M, Kieffer S, Curt A, Curt R, Bastien O, Coute Y, Pelloux H, Hakimi MA |
| Citation(s) |
23601110 |
| |
| Submission date |
Jun 18, 2012 |
| Last update date |
Nov 01, 2017 |
| Contact name |
Mohamed-ali HAKIMI |
| E-mail(s) |
mohamed-ali.hakimi@univ-grenoble-alpes.fr
|
| Phone |
(33)476637469
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| Organization name |
CNRS
|
| Department |
UMR5309
|
| Lab |
IAB - HAKIMI Team
|
| Street address |
Domaine de la Merci, Campus Santé
|
| City |
LA TRONCHE |
| State/province |
Grenoble |
| ZIP/Postal code |
38700 |
| Country |
France |
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| Platforms (2) |
| GPL10191 |
NimbleGen Homo sapiens HG18 090828 opt expr HX12 (12x135k) |
| GPL11202 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version) |
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| Samples (6)
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| GSM945860 |
GRA16-dependent host transcriptional responses in mouse BMDM infected with T. gondii [RH_GRA16-KO] |
| GSM946926 |
GRA16-dependent host transcriptional responses in mouse BMDM infected with T. gondii [Pru_GRA16-KO] |
| GSM947409 |
GRA16-dependent host transcriptional responses HFF infected with T. gondii [RH_GRA16-KO] |
| GSM949319 |
Host transcriptional responses in mouse BMDM infected with T. gondii [Pru_WT] |
| GSM949320 |
Host transcriptional responses in mouse BMDM infected with T. gondii [RH_WT] |
| GSM949329 |
GRA16-dependent host transcriptional responses HFF infected with T. gondii [RH_WT] |
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| Relations |
| BioProject |
PRJNA168971 |
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