Gatekeeper role of 14-3-3tau protein in HIV-1 gp120-mediated apoptosis of human endothelial cells by inactivation of Bad

AIDS. 2007 May 11;21(8):911-20. doi: 10.1097/QAD.0b013e32810539f3.


Objective: HIV-1-associated dementia (HAD) is a major neurological complication often observed in the advanced stages of AIDS. We have reported that 14-3-3 proteins in cerebrospinal fluid, reflecting neuronal cell destruction, is a real-time marker of HAD progression. This study was designed to examine the role of 14-3-3 proteins in HAD.

Design: An in-vitro human umbilical vein endothelial cells (HUVEC) model of gp120 protein-induced apoptosis to study the protective role of 14-3-3 in HIV-1 gp120/CXCR4-mediated cell death.

Methods: The alpha-chemokine receptor-mediated cell death by HIV-1 envelope protein, gp120, the critical event that causes neuron loss and endothelial cell injury, was evaluated in HUVEC undergoing gp120-induced apoptosis through the CXCR4 receptor. We studied the effects of siRNA for each 14-3-3 isoform on the death of HUVEC treated with CXCR4-preferring gp120 (IIIB).

Results: Gp120 increased the expression of 14-3-3tau in HUVEC. The binding of Gp120 to CXCR4 induced apoptosis of HUVEC through decreased binding of 14-3-3tau to the pro-apoptotic molecule, Bad. Treatment of the cells with dsRNA against 14-3-3tau enhanced the gp120-mediated dephosphorylation of Bad and its association with Bcl-XL in mitochondria, accelerating the gp120-induced apoptosis, whereas suppression of Bad by RNAi rescued the cells from apoptosis triggered by gp120.

Conclusions: The specific up-regulation of 14-3-3tau in HUVEC negatively regulated gp120/CXCR4-mediated cell death by protecting Bad dephosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / biosynthesis
  • 14-3-3 Proteins / physiology*
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Cells, Cultured
  • Cytochromes c / metabolism
  • Cytosol / metabolism
  • Down-Regulation / drug effects
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • HIV Envelope Protein gp120 / pharmacology*
  • HIV Envelope Protein gp120 / physiology
  • HIV Envelope Protein gp160 / pharmacology
  • Humans
  • Mitochondria / metabolism
  • Phosphorylation / drug effects
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Translocation, Genetic
  • Up-Regulation / drug effects
  • bcl-Associated Death Protein / metabolism
  • bcl-Associated Death Protein / physiology*


  • 14-3-3 Proteins
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp160
  • Recombinant Proteins
  • bcl-Associated Death Protein
  • Cytochromes c