53BP1 represses mitotic catastrophe in syncytia elicited by the HIV-1 envelope

J. L. Perfettini, R. Nardacci, C. Séror, S. Q. Raza, S. Sepe, H. Sadi, F. Brottes, A. Amendola, F. Subra, F. Del Nonno, L. Chessa, A. D'Incecco, M. L. Gougeon, M. Piacentini, G. Kroemer

Research output: Contribution to journalArticle

Abstract

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)). It colocalizes partially with the promyelomonocytic leukemia protein (PML), and the ataxia telangiectasia mutated kinase (ATM), the two components of the DDR that mediate apoptosis induced by the HIV-1 envelope. ATM-dependent phosphorylation of 53BP1 on serines 25 and 1778 (53BP1S25P and 53BP1S1778P) occurs at these DNA damage foci. 53BP1S25P was also detected in syncytia present in the lymph nodes or frontal brain sections from HIV-1-infected carriers, as well as in peripheral blood mononucleated cells from HIV-1-infected individuals, correlating with viral load. Knockdown of 53BP1 caused HIV-1 envelope-induced syncytia to enter abnormal mitoses, leading to their selective destruction through mitochondrion-dependent and caspase-dependent pathways. In conclusion, depletion of 53BP1 triggers the demise of HIV-1-elicited syncytia through mitotic catastrophe.

Original languageEnglish
Pages (from-to)811-820
Number of pages10
JournalCell Death and Differentiation
Volume17
Issue number5
DOIs
Publication statusPublished - May 2010

Fingerprint

Giant Cells
HIV-1
DNA Damage
Mitosis
Nuclear Fusion
Phosphotransferases
Ataxia Telangiectasia Mutated Proteins
Ataxia Telangiectasia
Caspases
Viral Load
Serine
Blood Cells
Carrier Proteins
Mitochondria
Leukemia
Lymph Nodes
Phosphorylation
Apoptosis
Brain

Keywords

  • AIDS
  • Apoptosis
  • ATM
  • DNA damage response
  • PML

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Perfettini, J. L., Nardacci, R., Séror, C., Raza, S. Q., Sepe, S., Sadi, H., ... Kroemer, G. (2010). 53BP1 represses mitotic catastrophe in syncytia elicited by the HIV-1 envelope. Cell Death and Differentiation, 17(5), 811-820. https://doi.org/10.1038/cdd.2009.159

53BP1 represses mitotic catastrophe in syncytia elicited by the HIV-1 envelope. / Perfettini, J. L.; Nardacci, R.; Séror, C.; Raza, S. Q.; Sepe, S.; Sadi, H.; Brottes, F.; Amendola, A.; Subra, F.; Del Nonno, F.; Chessa, L.; D'Incecco, A.; Gougeon, M. L.; Piacentini, M.; Kroemer, G.

In: Cell Death and Differentiation, Vol. 17, No. 5, 05.2010, p. 811-820.

Research output: Contribution to journalArticle

Perfettini, JL, Nardacci, R, Séror, C, Raza, SQ, Sepe, S, Sadi, H, Brottes, F, Amendola, A, Subra, F, Del Nonno, F, Chessa, L, D'Incecco, A, Gougeon, ML, Piacentini, M & Kroemer, G 2010, '53BP1 represses mitotic catastrophe in syncytia elicited by the HIV-1 envelope', Cell Death and Differentiation, vol. 17, no. 5, pp. 811-820. https://doi.org/10.1038/cdd.2009.159
Perfettini, J. L. ; Nardacci, R. ; Séror, C. ; Raza, S. Q. ; Sepe, S. ; Sadi, H. ; Brottes, F. ; Amendola, A. ; Subra, F. ; Del Nonno, F. ; Chessa, L. ; D'Incecco, A. ; Gougeon, M. L. ; Piacentini, M. ; Kroemer, G. / 53BP1 represses mitotic catastrophe in syncytia elicited by the HIV-1 envelope. In: Cell Death and Differentiation. 2010 ; Vol. 17, No. 5. pp. 811-820.
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