Different molecular mechanisms of HTLV-1 and HIV LTR activation by TPA

Azhar Jabareen, Manal Suleman, Aya Abu-Jaafar, Mahmoud Huleihel

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

HTLV-1 and HIV-1 are retroviruses involved in different human diseases. However, following infection, these viruses inter into a latent state. Tax and Tat are regarded as trans-activators of HTLV-1 and HIV-1 respectively. As it known, during the latent state the infected cells contain low Tax and Tat protein levels, so the activation of these viruses must be independent of these proteins. Here we focus on exploring the mechanism of activation of these viruses by 12-O-tetradecanoylphorbol-13-acetate (TPA), which is a potent activator of protein kinase C (PKC) and considered as a stress-inducing agent. Our results showed that short exposure to TPA considerably stimulated only the HIV-1 LTR expression, while long exposure stimulated only the HTLV-1 LTR and that their activation is agonized or antagonized by PKC respectively. It was found that TPA induced interaction between the transcriptional factors Sp1 and P53 producing Sp1-p53 complex which strongly interacted with c-Jun only after short exposure to TPA. In addition, TPA treatment highly induced the expression of CREB which attached to the Sp1-p53 complex mainly after a long exposure to TPA. A strong binding of sp1, p53 and CREB proteins with HTLV-1 LTR and strong binding of NF-κB with HIV-1 LTR were observed after long (24 h) and short (6 h) exposures to TPA respectively by Chip assay. These results support the possibility that sp1, p53 and CREB are involved in the TPA induced HTLV-1 LTR expression while TPA activation of HIV-1 LTR seems to be dependent on PKC activity through the NF-κB pathway.

Original languageEnglish
Pages (from-to)538-543
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume500
Issue number3
DOIs
StatePublished - 7 Jun 2018

Keywords

  • HIV-1 LTR
  • HTLV-1 LTR
  • Jurkat cell line
  • NF-κB site
  • PKC isoforms
  • Sp1 site
  • TPA

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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