Protein Kinase D3 Is Essential for Prostratin-Activated Transcription of Integrated HIV-1 Provirus Promoter via NF-κB Signaling Pathway. (20th July 2014)

• Record Type: Journal Article
• Authors: Wang, Huiping; Zhu, Xinxing; Zhu, Ying; Liu, Jiangfang; Hu, Xiangming; Wang, Yu; Peng, Sijia; Chen, Yanheng; Chen, Ruichuan; Ding, Feng; Liu, Runzhong
• Other Names: Oster Henrik Academic Editor.
• Is Part Of: BioMed research international. Volume 2014(2014)
• Publication Date: 2014-07-20
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Life sciences -- Periodicals; 610.5
• DOI: 10.1155/2014/968027
• Languages: English
• ISSNs: 2314-6133

Abstract

Abstract : Prostratin has been proposed as a promising reagent for eradicating the latent HIV-1 provirus by inducing HIV-1 transcription activation. The molecular mechanism of this activation, however, is far from clear. Here, we show that the protein kinase D3 (PKD3) is essential for prostratin-induced transcription activation of latent HIV-1 provirus. First, silencing PKD3, but not the other members of PKD family, blocked prostratin-induced transcription of HIV-1. Second, overexpressing the constitutively active form of PKD3, but not the wild-type or kinase-dead form of PKD3, augmented the expression of HIV-1. Consistent with this observation, we found that prostratin could trigger PKD3 activation by inducing the phosphorylation of its activation loop. In addition, we identified PKCε of the novel PKC subfamily as the upstream kinase for this phosphorylation. Finally, the activation effect of PKD3 on HIV-1 transcription was shown to depend on the presence of κ B element and the prostratin-induced activation of NF- κ B, as indicated by the fact that silencing PKD3 blocked prostratin-induced NF- κ B activation and NF- κ B-dependent HIV-1 transcription. Therefore, for the first time, PKD3 is implicated in the transcription activation of latent HIV-1 provirus, and our results revealed a molecular mechanism of prostratin-induced HIV-1 transcription via PKCε /PKD3/NF- κ B signaling pathway.