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Astrocyte apoptosis induced by HIV-1 transactivation of the c-kit protooncogene.

Publication ,  Journal Article
He, J; deCastro, CM; Vandenbark, GR; Busciglio, J; Gabuzda, D
Published in: Proc Natl Acad Sci U S A
April 15, 1997

HIV-1 infection of the central nervous system (CNS) frequently causes dementia and other neurological disorders. The mechanisms of CNS injury in HIV-1 infection are poorly understood. Apoptosis of neurons and astrocytes is induced by HIV-1 infection in vitro and in brain tissue from AIDS patients, but the apoptotic stimuli have not been identified. We report herein that HIV-1 infection of primary brain cultures induces the receptor tyrosine kinase protooncogene c-kit and that high levels of c-Kit expression are associated with astrocyte apoptosis. Overexpression of c-Kit in an astrocyte-derived cell line in the absence of HIV-1 induces rapid apoptotic death. The apoptotic mechanism requires the c-Kit tyrosine kinase domain. The mechanism of c-kit induction by HIV-1 involves transactivation of the c-kit promoter by the HIV-1 Nef protein. These studies demonstrate that c-Kit can induce astrocyte apoptosis and suggest that this mechanism may play a role in CNS injury caused by HIV-1 infection. We propose that c-Kit can serve dual functions as a growth factor receptor or apoptosis inducer.

Duke Scholars

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

April 15, 1997

Volume

94

Issue

8

Start / End Page

3954 / 3959

Location

United States

Related Subject Headings

  • Proto-Oncogene Proteins c-kit
  • Humans
  • HIV-1
  • HIV Infections
  • Cells, Cultured
  • Astrocytes
  • Apoptosis
 

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He, J., deCastro, C. M., Vandenbark, G. R., Busciglio, J., & Gabuzda, D. (1997). Astrocyte apoptosis induced by HIV-1 transactivation of the c-kit protooncogene. Proc Natl Acad Sci U S A, 94(8), 3954–3959. https://doi.org/10.1073/pnas.94.8.3954
He, J., C. M. deCastro, G. R. Vandenbark, J. Busciglio, and D. Gabuzda. “Astrocyte apoptosis induced by HIV-1 transactivation of the c-kit protooncogene.Proc Natl Acad Sci U S A 94, no. 8 (April 15, 1997): 3954–59. https://doi.org/10.1073/pnas.94.8.3954.
He J, deCastro CM, Vandenbark GR, Busciglio J, Gabuzda D. Astrocyte apoptosis induced by HIV-1 transactivation of the c-kit protooncogene. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3954–9.
He, J., et al. “Astrocyte apoptosis induced by HIV-1 transactivation of the c-kit protooncogene.Proc Natl Acad Sci U S A, vol. 94, no. 8, Apr. 1997, pp. 3954–59. Pubmed, doi:10.1073/pnas.94.8.3954.
He J, deCastro CM, Vandenbark GR, Busciglio J, Gabuzda D. Astrocyte apoptosis induced by HIV-1 transactivation of the c-kit protooncogene. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3954–3959.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

April 15, 1997

Volume

94

Issue

8

Start / End Page

3954 / 3959

Location

United States

Related Subject Headings

  • Proto-Oncogene Proteins c-kit
  • Humans
  • HIV-1
  • HIV Infections
  • Cells, Cultured
  • Astrocytes
  • Apoptosis