Skip to main content
The tumor suppressor protein PML controls apoptosis induced by the HIV-1 envelope
Cell Death and Differentiation
  • Jean-Luc Perfettini, Université Paris
  • Roberta Nardacci, National Institute for Infectious Diseases
  • C. Séror, Université Paris Sud
  • M. Bourouba, Université Paris Sud
  • F. Subra, Ecole Normale Supérieure de Cachan
  • L. Gros, Ecole Normale Supérieure de Cachan
  • Gwenola Manic, Université Paris Sud
  • A. Amendola, National Institute for Infectious Diseases
  • P. Masdehors, Institut Pasteur
  • F. Rosselli, Université Paris Sud
  • David M. Ojcius, University of California, Merced
  • C. Auclair, Ecole Normale Supérieure de Cachan
  • H. de Thé, Université de Paris
  • M. L. Gougeon, Institut Pasteur
  • M. Piacentini, National Institute for Infectious Diseases
  • G. Kroemer, Université Paris Sud
David M. Ojcius: 0000-0003-1461-4495
Document Type
Publication Date
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. The aggregation of PML was detectable in syncytia present in the brain or lymph nodes from patients with HIV-1 infection, as well as in a fraction of blood leukocytes, correlating with viral status. Using a range of specific inhibitors of PML (the oncogenic PML/RARα fusion product or specific small interfering RNAs), we demonstrated that, in Env-elicited syncytia, PML was required for activating phosphorylation of ataxia telangiectasia mutated (ATM), which colocalized with PML in nuclear bodies, in a molecular complex that also involved topoisomerase IIβ-binding protein 1. PML knockdown thus inhibited the ATM-dependent DNA damage response that culminates in the activation of p53, p53-dependent transcription of pro-apoptotic genes and cell death. Infection of CD4-expressing cells with HIV-1 also induced syncytial apoptosis, which could be suppressed by inhibiting PML. Altogether, these data indicate that PML activation is a critical early event that participates in the apoptotic demise of HIV-1-elicited syncytia.
Citation Information
Jean-Luc Perfettini, Roberta Nardacci, C. Séror, M. Bourouba, et al.. "The tumor suppressor protein PML controls apoptosis induced by the HIV-1 envelope" Cell Death and Differentiation Vol. 16 Iss. 2 (2009) p. 298 - 311 ISSN: 1350-9047
Available at: