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53BP1 represses mitotic catastrophe in syncytia elicited by the HIV-1 envelope.
Cell Death Differ
May 2010
INSERM U, Villejuif, France.
p53 binding protein-1 (53BP1) participates in checkpoint signaling during the DNA damage response (DDR) and during mitosis. In this study we report that 53BP1 aggregates in nuclear foci within syncytia elicited by the human immunodeficiency virus (HIV)-1 envelope. 53BP1 aggregation occurs as a consequence of nuclear fusion (karyogamy (KG)).
View Article and Find Full Text PDFThe tumor suppressor protein PML controls apoptosis induced by the HIV-1 envelope.
Cell Death Differ
February 2009
INSERM U848, Institut Gustave Roussy, Université Paris Sud, Paris 11, 39 rue Camille-Desmoulins, F-94805 Villejuif, France.
Promyelomonocytic leukemia (PML) is a prominent oncosuppressor whose inactivation is involved in the pathogenesis of hematological and epithelial cancers. Here, we report that PML aggregated in nuclear bodies in syncytia elicited by the envelope glycoprotein complex (Env) of human immunodeficiency virus-1 (HIV-1) in vitro. PML aggregation occurred after the fusion of nuclei (karyogamy) within syncytia but before the apoptotic program was activated.
View Article and Find Full Text PDFEssential role of p53 phosphorylation by p38 MAPK in apoptosis induction by the HIV-1 envelope.
J Exp Med
January 2005
Centre National Recherche Scientifique-UMR8125, Institut Gustave Roussy, F-94805 Villejuif, France.
The proapoptotic activity of the transcription factor p53 critically depends on the phosphorylation of serine 46 (p53S46P). Here, we show that syncytia containing p53S46P could be detected in lymph node biopsies from human immunodeficiency virus (HIV)-1 carriers, in the brain of patients with HIV-1-associated dementia and in cocultures of HeLa expressing the HIV-1 envelope glycoprotein complex (Env) with HeLa cells expressing CD4. In this latter model, cell death was the result of a sequential process involving cell fusion, nuclear fusion (karyogamy), phosphorylation of serine 15 (p53S15P), later on serine 46 (p53S46P), and transcription of p53 target genes.
View Article and Find Full Text PDFSequential involvement of Cdk1, mTOR and p53 in apoptosis induced by the HIV-1 envelope.
EMBO J
August 2002
Centre National de la Recherche Scientifique, UMR1599, Institut Gustave Roussy, 39 rue Camille-Desmoulins, F-94805 Villejuif, , France.
Syncytia arising from the fusion of cells expressing the HIV-1-encoded Env gene with cells expressing the CD4/CXCR4 complex undergo apoptosis following the nuclear translocation of mammalian target of rapamycin (mTOR), mTOR-mediated phosphorylation of p53 on Ser15 (p53(S15)), p53-dependent upregulation of Bax and activation of the mitochondrial death pathway. p53(S15) phosphorylation is only detected in syncytia in which nuclear fusion (karyogamy) has occurred. Karyogamy is secondary to a transient upregulation of cyclin B and a mitotic prophase-like dismantling of the nuclear envelope.
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