DNA dependent protein kinase (DNA-PK) enhances HIV transcription by promoting RNA polymerase II activity and recruitment of transcription machinery at HIV LTR

Oncotarget
Sonia ZicariMudit Tyagi

Abstract

Despite reductions in mortality from the use of highly active antiretroviral therapy (HAART), the presence of latent or transcriptionally silent proviruses prevents HIV cure/eradication. We have previously reported that DNA-dependent protein kinase (DNA-PK) facilitates HIV transcription by interacting with the RNA polymerase II (RNAP II) complex recruited at HIV LTR. In this study, using different cell lines and peripheral blood mononuclear cells (PBMCs) of HIV-infected patients, we found that DNA-PK stimulates HIV transcription at several stages, including initiation, pause-release and elongation. We are reporting for the first time that DNA-PK increases phosphorylation of RNAP II C-terminal domain (CTD) at serine 5 (Ser5) and serine 2 (Ser2) by directly catalyzing phosphorylation and by augmenting the recruitment of the positive transcription elongation factor (P-TEFb) at HIV LTR. Our findings suggest that DNA-PK expedites the establishment of euchromatin structure at HIV LTR. DNA-PK inhibition/knockdown leads to the severe impairment of HIV replication and reactivation of latent HIV provirus. DNA-PK promotes the recruitment of Tripartite motif-containing 28 (TRIM28) at LTR and assists the release of paused RNAP II through TR...Continue Reading

References

Dec 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·A DvirW S Dynan
Dec 1, 1990·Molecular and Cellular Biology·T CarterS DeLeon
Jun 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·Y OhosoneJ A Hardin
Jan 1, 1988·Progress in Nucleic Acid Research and Molecular Biology·J F Ward
Apr 4, 1995·Biochimica Et Biophysica Acta·M E Dahmus
Jan 1, 1996·Current Topics in Microbiology and Immunology·C W Anderson, T H Carter
Nov 1, 1996·Genes & Development·G OrphanidesD Reinberg
Apr 18, 1998·The Journal of Biological Chemistry·S TrigonM Morange
Aug 1, 1998·Biochimica Et Biophysica Acta·H ShenK D Tew
Nov 30, 1999·Nature·T W ChunA S Fauci
Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·R T DaveyH C Lane
Mar 25, 2000·Molecular and Cellular Biology·D H Price
Nov 30, 2000·Gene Expression·T Riedl, J M Egly
Sep 22, 2001·Endocrine-related Cancer·R C Stein
Aug 4, 2006·Molecular Cell·B Matija Peterlin, David H Price
Aug 29, 2006·Nature Reviews. Molecular Cell Biology·Abbie SaundersJohn T Lis
Nov 17, 2007·The EMBO Journal·Mudit Tyagi, Jonathan Karn
Sep 17, 2008·Oncogene·T L Yuan, L C Cantley
Mar 3, 2010·Free Radical Biology & Medicine·Prakash PeddiAlexandros G Georgakilas
Apr 29, 2010·Current HIV/AIDS Reports·David M Margolis
May 25, 2010·Biochemical and Biophysical Research Communications·Hongbing LiuAndrew P Rice

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Citations

Aug 23, 2020·Cells·Andrey AnisenkoMarina Gottikh
Dec 22, 2020·Expert Opinion on Therapeutic Patents·Suwen HuTian Xie
Apr 11, 2021·Nature Cell Biology·Aline Marnef, Gaëlle Legube
May 1, 2021·International Journal of Molecular Sciences·Joseph HokelloMudit Tyagi
Jul 3, 2021·Pathogens·Adhikarimayum Lakhikumar SharmaMudit Tyagi

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Methods Mentioned

BETA
nuclear translocation
immunoprecipitation
ChIP
PCR
acetylation
electrophoresis
fluorescence-activated cell sorting

Software Mentioned

GraphPad Prism
ImageJ
Excel
Blast

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