Kalantari, Parisa ; Narayan, Vivek ; Natarajan, Sathish K. ; Muralidhar, Kambadur ; Gandhi, Ujjawal H. ; Vunta, Hema ; Henderson, Andrew J. ; Prabhu, K. Sandeep (2008) Thioredoxin reductase-1 negatively regulates HIV-1 transactivating protein Tat-dependent transcription in human macrophages Journal of Biological Chemistry, 283 (48). pp. 33183-33190. ISSN 0021-9258
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Official URL: http://www.jbc.org/content/283/48/33183.short
Related URL: http://dx.doi.org/10.1074/jbc.M807403200
Abstract
Epidemiological studies suggest a correlation between severity of acquired immunodeficiency syndrome (AIDS) and selenium deficiency, indicating a protective role for this anti-oxidant during HIV infection. Here we demonstrate that thioredoxin reductase-1 (TR1), a selenium-containing pyridine nucleotide-disulfide oxidoreductase that reduces protein disulfides to free thiols, negatively regulates the activity of the HIV-1 encoded transcriptional activator, Tat, in human macrophages. We used a small interfering RNA approach as well as a high affinity substrate of TR1, ebselen, to demonstrate that Tat-dependent transcription and HIV-1 replication were significantly increased in human macrophages when TR1 activity was reduced. The increase in HIV-1 replication in TR1 small interfering RNA-treated cells was independent of the redox-sensitive transcription factor, NF-κB. These studies indicate that TR-1 acts as a negative regulator of Tat-dependent transcription. Furthermore, in vitro biochemical assays with recombinant Tat protein confirmed that TR1 targets two disulfide bonds within the Cys-rich motif required for efficient HIV-1 transactivation. Increasing TR1 expression along with other selenoproteins by supplementing with selenium suggests a potential inexpensive adjuvant therapy for HIV/AIDS patients.
Item Type: | Article |
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Source: | Copyright of this article belongs to The American Society for Biochemistry and Molecular Biology. |
ID Code: | 36070 |
Deposited On: | 14 Apr 2011 14:14 |
Last Modified: | 17 May 2016 19:01 |
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