Accession Number:

ADA415803

Title:

Induction of Apoptosis by Targeting the Microtubule Network: Using HIV Tat as a Model System

Descriptive Note:

Annual summary rept. 18 Mar 2002-17 Mar 2003

Corporate Author:

CALIFORNIA UNIV BERKELEY

Personal Author(s):

Report Date:

2003-04-01

Pagination or Media Count:

15.0

Abstract:

Depletion of CD4 T cells is the hallmark of HIV Infection and AIDS progression. In addition to the direct killing of the viral-infected cells, HIV infection also leads to increased apoptosis of predominantly uninfected bystander cells. This is mediated in part through the HIV-1 Tat protein, which is secreted by the infected cells and taken up by uninfected cells. Using an affinity-purification approach, a specific and direct interaction of Tat with tubulin and polymerized microtubules has been detected. This interaction does not affect the secretion and uptake of Tat but is critical for Tat to induce apoptosis. Tat binds tubulinimicrotubules through a four-amino-acid sub-domain of its conserved core region, leading to the alteration of microtubule dynamics and activation of a mitochondria-dependent apoptotic pathway. Bim, a pro-apoptotic Bcl-2 relative and a transducer of death signals initiated by perturbation of microtubule dynamics, facilitates the Tat-induced apoptosis. Our findings reveal a strategy by which Tat induces apoptosis by targeting the microtubule network, sharing a similar apoptotic pathway with the commonly used breast cancer drug Taxol.

Subject Categories:

  • Medicine and Medical Research
  • Microbiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE