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Host cell subversion by Toxoplasma GRA16, an exported dense granule protein that targets the host cell nucleus and alters gene expression.

Abstract：

: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.

journal_name

Cell Host Microbe

journal_title

Cell host & microbe

authors

Bougdour A,Durandau E,Brenier-Pinchart MP,Ortet P,Barakat M,Kieffer S,Curt-Varesano A,Curt-Bertini RL,Bastien O,Coute Y,Pelloux H,Hakimi MA

doi

10.1016/j.chom.2013.03.002

subject

Has Abstract

pub_date

2013-04-17 00:00:00

pages

489-500

issue

4

eissn

1931-3128

issn

1934-6069

pii

S1931-3128(13)00112-1

journal_volume

13

pub_type

杂志文章

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