Gene interactions and pathways from curated databases and text-mining
EMBO J 2002, PMID: 12145207

Sequential involvement of Cdk1, mTOR and p53 in apoptosis induced by the HIV-1 envelope.

Castedo, Maria; Roumier, Thomas; Blanco, Julià; Ferri, Karine F; Barretina, Jordi; Tintignac, Lionel A; Andreau, Karine; Perfettini, Jean-Luc; Amendola, Alessandra; Nardacci, Roberta; Leduc, Philip; Ingber, Donald E; Druillennec, Sabine; Roques, Bernard; Leibovitch, Serge A; Vilella-Bach, Montserrat; Chen, Jie; Este, José A; Modjtahedi, Nazanine; Piacentini, Mauro; Kroemer, Guido

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. Inhibition of cyclin-dependent kinase-1 (Cdk1) prevents karyogamy, mTOR activation, p53(S15) phosphorylation and apoptosis. Neutralization of p53 fails to prevent karyogamy, yet suppresses apoptosis. Peripheral blood mononuclear cells from HIV-1-infected patients exhibit an increase in cyclin B and mTOR expression, correlating with p53(S15) phosphorylation and viral load. Cdk1 inhibition prevents the death of syncytia elicited by HIV-1 infection of primary CD4 lymphoblasts. Thus, HIV-1 elicits a pro-apoptotic signal transduction pathway relying on the sequential action of cyclin B-Cdk1, mTOR and p53.

Diseases/Pathways annotated by Medline MESH: HIV Infections
Document information provided by NCBI PubMed

Text Mining Data

p53 → mTOR: " 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 "

Bax → p53: " 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 "

Manually curated Databases

No curated data.