HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Ivanov, A., Lin, X., Ammosova, T., Ilatovskiy, A., Kumari, N., Lassiter, H., Afangbedji, N., Niu, X., Petukhov, M., & Nekhai, S. Retrovirology, 2018. cited By 4![HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Background: HIV-1 transcription activator protein Tat is phosphorylated in vitro by CDK2 and DNA-PK on Ser-16 residue and by PKR on Tat Ser-46 residue. Here we analyzed Tat phosphorylation in cultured cells and its functionality. Results: Mass spectrometry analysis showed primarily Tat Ser-16 phosphorylation in cultured cells. In vitro, CDK2/cyclin E predominantly phosphorylated Tat Ser-16 and PKR-Tat Ser-46. Alanine mutations of either Ser-16 or Ser-46 decreased overall Tat phosphorylation. Phosphorylation of Tat Ser-16 was reduced in cultured cells treated by a small molecule inhibitor of CDK2 and, to a lesser extent, an inhibitor of DNA-PK. Conditional knock-downs of CDK2 and PKR inhibited and induced one round HIV-1 replication respectively. HIV-1 proviral transcription was inhibited by Tat alanine mutants and partially restored by S16E mutation. Pseudotyped HIV-1 with Tat S16E mutation replicated well, and HIV-1 Tat S46E-poorly, but no live viruses were obtained with Tat S16A or Tat S46A mutations. TAR RNA binding was affected by Tat Ser-16 alanine mutation. Binding to cyclin T1 showed decreased binding of all Ser-16 and Ser-46 Tat mutants with S16D and Tat S46D mutationts showing the strongest effect. Molecular modelling and molecular dynamic analysis revealed significant structural changes in Tat/CDK9/cyclin T1 complex with phosphorylated Ser-16 residue, but not with phosphorylated Ser-46 residue. Conclusion: Phosphorylation of Tat Ser-16 induces HIV-1 transcription, facilitates binding to TAR RNA and rearranges CDK9/cyclin T1/Tat complex. Thus, phosphorylation of Tat Ser-16 regulates HIV-1 transcription and may serve as target for HIV-1 therapeutics. © 2018 The Author(s).
@ARTICLE{Ivanov2018,
author={Ivanov, A. and Lin, X. and Ammosova, T. and Ilatovskiy, A.V. and Kumari, N. and Lassiter, H. and Afangbedji, N. and Niu, X. and Petukhov, M.G. and Nekhai, S.},
title={HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription},
journal={Retrovirology},
year={2018},
volume={15},
number={1},
doi={10.1186/s12977-018-0422-5},
art_number={39},
note={cited By 4},
url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85047482579&doi=10.1186%2fs12977-018-0422-5&partnerID=40&md5=80ac4eaa0e53385e032d2c6db96a912e},
affiliation={Howard University, Center for Sickle Cell Disease, 1840 7th Street, N.W. HURB1, Suite 202, Washington, DC 20001, United States; Howard University, Department of Medicine, Washington, DC, United States; Yakut Science Center for Complex Medical Problems, Yakutsk, Russian Federation; Petersburg Nuclear Physics Institute, Division of Molecular and Radiation Biophysics, Gatchina, Russian Federation; Research Center for Nanobiotechnologies, St. Petersburg, Russian Federation},
abstract={Background: HIV-1 transcription activator protein Tat is phosphorylated in vitro by CDK2 and DNA-PK on Ser-16 residue and by PKR on Tat Ser-46 residue. Here we analyzed Tat phosphorylation in cultured cells and its functionality. Results: Mass spectrometry analysis showed primarily Tat Ser-16 phosphorylation in cultured cells. In vitro, CDK2/cyclin E predominantly phosphorylated Tat Ser-16 and PKR-Tat Ser-46. Alanine mutations of either Ser-16 or Ser-46 decreased overall Tat phosphorylation. Phosphorylation of Tat Ser-16 was reduced in cultured cells treated by a small molecule inhibitor of CDK2 and, to a lesser extent, an inhibitor of DNA-PK. Conditional knock-downs of CDK2 and PKR inhibited and induced one round HIV-1 replication respectively. HIV-1 proviral transcription was inhibited by Tat alanine mutants and partially restored by S16E mutation. Pseudotyped HIV-1 with Tat S16E mutation replicated well, and HIV-1 Tat S46E-poorly, but no live viruses were obtained with Tat S16A or Tat S46A mutations. TAR RNA binding was affected by Tat Ser-16 alanine mutation. Binding to cyclin T1 showed decreased binding of all Ser-16 and Ser-46 Tat mutants with S16D and Tat S46D mutationts showing the strongest effect. Molecular modelling and molecular dynamic analysis revealed significant structural changes in Tat/CDK9/cyclin T1 complex with phosphorylated Ser-16 residue, but not with phosphorylated Ser-46 residue. Conclusion: Phosphorylation of Tat Ser-16 induces HIV-1 transcription, facilitates binding to TAR RNA and rearranges CDK9/cyclin T1/Tat complex. Thus, phosphorylation of Tat Ser-16 regulates HIV-1 transcription and may serve as target for HIV-1 therapeutics. © 2018 The Author(s).},
funding_details={National Heart, Lung, and Blood InstituteNIDA},
funding_details={District of Columbia Developmental Center for AIDS ResearchAI117970},
funding_details={Российский Фонд Фундаментальных Исследований (РФФИ)12-04-91444-NIZ},
funding_details={NIH Blueprint for Neuroscience Research1R01HL125005, U19AI109664, P30AI117970, 1P50HL118006, 1UM1AI26617, 5G12MD007597},
funding_details={Ministry of Education and Science of the Russian Federation2012-1.5-12-000-1001-030},
}
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{"_id":"rYYoStSmEtoLpRA45","bibbaseid":"ivanov-lin-ammosova-ilatovskiy-kumari-lassiter-afangbedji-niu-etal-hiv1tatphosphorylationonser16residuemodulateshiv1transcription-2018","author_short":["Ivanov, A.","Lin, X.","Ammosova, T.","Ilatovskiy, A.","Kumari, N.","Lassiter, H.","Afangbedji, N.","Niu, X.","Petukhov, M.","Nekhai, S."],"bibdata":{"bibtype":"article","type":"article","author":[{"propositions":[],"lastnames":["Ivanov"],"firstnames":["A."],"suffixes":[]},{"propositions":[],"lastnames":["Lin"],"firstnames":["X."],"suffixes":[]},{"propositions":[],"lastnames":["Ammosova"],"firstnames":["T."],"suffixes":[]},{"propositions":[],"lastnames":["Ilatovskiy"],"firstnames":["A.V."],"suffixes":[]},{"propositions":[],"lastnames":["Kumari"],"firstnames":["N."],"suffixes":[]},{"propositions":[],"lastnames":["Lassiter"],"firstnames":["H."],"suffixes":[]},{"propositions":[],"lastnames":["Afangbedji"],"firstnames":["N."],"suffixes":[]},{"propositions":[],"lastnames":["Niu"],"firstnames":["X."],"suffixes":[]},{"propositions":[],"lastnames":["Petukhov"],"firstnames":["M.G."],"suffixes":[]},{"propositions":[],"lastnames":["Nekhai"],"firstnames":["S."],"suffixes":[]}],"title":"HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription","journal":"Retrovirology","year":"2018","volume":"15","number":"1","doi":"10.1186/s12977-018-0422-5","art_number":"39","note":"cited By 4","url":"https://www.scopus.com/inward/record.uri?eid=2-s2.0-85047482579&doi=10.1186%2fs12977-018-0422-5&partnerID=40&md5=80ac4eaa0e53385e032d2c6db96a912e","affiliation":"Howard University, Center for Sickle Cell Disease, 1840 7th Street, N.W. HURB1, Suite 202, Washington, DC 20001, United States; Howard University, Department of Medicine, Washington, DC, United States; Yakut Science Center for Complex Medical Problems, Yakutsk, Russian Federation; Petersburg Nuclear Physics Institute, Division of Molecular and Radiation Biophysics, Gatchina, Russian Federation; Research Center for Nanobiotechnologies, St. Petersburg, Russian Federation","abstract":"Background: HIV-1 transcription activator protein Tat is phosphorylated in vitro by CDK2 and DNA-PK on Ser-16 residue and by PKR on Tat Ser-46 residue. Here we analyzed Tat phosphorylation in cultured cells and its functionality. Results: Mass spectrometry analysis showed primarily Tat Ser-16 phosphorylation in cultured cells. In vitro, CDK2/cyclin E predominantly phosphorylated Tat Ser-16 and PKR-Tat Ser-46. Alanine mutations of either Ser-16 or Ser-46 decreased overall Tat phosphorylation. Phosphorylation of Tat Ser-16 was reduced in cultured cells treated by a small molecule inhibitor of CDK2 and, to a lesser extent, an inhibitor of DNA-PK. Conditional knock-downs of CDK2 and PKR inhibited and induced one round HIV-1 replication respectively. HIV-1 proviral transcription was inhibited by Tat alanine mutants and partially restored by S16E mutation. Pseudotyped HIV-1 with Tat S16E mutation replicated well, and HIV-1 Tat S46E-poorly, but no live viruses were obtained with Tat S16A or Tat S46A mutations. TAR RNA binding was affected by Tat Ser-16 alanine mutation. Binding to cyclin T1 showed decreased binding of all Ser-16 and Ser-46 Tat mutants with S16D and Tat S46D mutationts showing the strongest effect. Molecular modelling and molecular dynamic analysis revealed significant structural changes in Tat/CDK9/cyclin T1 complex with phosphorylated Ser-16 residue, but not with phosphorylated Ser-46 residue. Conclusion: Phosphorylation of Tat Ser-16 induces HIV-1 transcription, facilitates binding to TAR RNA and rearranges CDK9/cyclin T1/Tat complex. Thus, phosphorylation of Tat Ser-16 regulates HIV-1 transcription and may serve as target for HIV-1 therapeutics. © 2018 The Author(s).","funding_details":"Ministry of Education and Science of the Russian Federation2012-1.5-12-000-1001-030","bibtex":"@ARTICLE{Ivanov2018,\r\nauthor={Ivanov, A. and Lin, X. and Ammosova, T. and Ilatovskiy, A.V. and Kumari, N. and Lassiter, H. and Afangbedji, N. and Niu, X. and Petukhov, M.G. and Nekhai, S.},\r\ntitle={HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription},\r\njournal={Retrovirology},\r\nyear={2018},\r\nvolume={15},\r\nnumber={1},\r\ndoi={10.1186/s12977-018-0422-5},\r\nart_number={39},\r\nnote={cited By 4},\r\nurl={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85047482579&doi=10.1186%2fs12977-018-0422-5&partnerID=40&md5=80ac4eaa0e53385e032d2c6db96a912e},\r\naffiliation={Howard University, Center for Sickle Cell Disease, 1840 7th Street, N.W. HURB1, Suite 202, Washington, DC 20001, United States; Howard University, Department of Medicine, Washington, DC, United States; Yakut Science Center for Complex Medical Problems, Yakutsk, Russian Federation; Petersburg Nuclear Physics Institute, Division of Molecular and Radiation Biophysics, Gatchina, Russian Federation; Research Center for Nanobiotechnologies, St. Petersburg, Russian Federation},\r\nabstract={Background: HIV-1 transcription activator protein Tat is phosphorylated in vitro by CDK2 and DNA-PK on Ser-16 residue and by PKR on Tat Ser-46 residue. Here we analyzed Tat phosphorylation in cultured cells and its functionality. Results: Mass spectrometry analysis showed primarily Tat Ser-16 phosphorylation in cultured cells. In vitro, CDK2/cyclin E predominantly phosphorylated Tat Ser-16 and PKR-Tat Ser-46. Alanine mutations of either Ser-16 or Ser-46 decreased overall Tat phosphorylation. Phosphorylation of Tat Ser-16 was reduced in cultured cells treated by a small molecule inhibitor of CDK2 and, to a lesser extent, an inhibitor of DNA-PK. Conditional knock-downs of CDK2 and PKR inhibited and induced one round HIV-1 replication respectively. HIV-1 proviral transcription was inhibited by Tat alanine mutants and partially restored by S16E mutation. Pseudotyped HIV-1 with Tat S16E mutation replicated well, and HIV-1 Tat S46E-poorly, but no live viruses were obtained with Tat S16A or Tat S46A mutations. TAR RNA binding was affected by Tat Ser-16 alanine mutation. Binding to cyclin T1 showed decreased binding of all Ser-16 and Ser-46 Tat mutants with S16D and Tat S46D mutationts showing the strongest effect. Molecular modelling and molecular dynamic analysis revealed significant structural changes in Tat/CDK9/cyclin T1 complex with phosphorylated Ser-16 residue, but not with phosphorylated Ser-46 residue. Conclusion: Phosphorylation of Tat Ser-16 induces HIV-1 transcription, facilitates binding to TAR RNA and rearranges CDK9/cyclin T1/Tat complex. Thus, phosphorylation of Tat Ser-16 regulates HIV-1 transcription and may serve as target for HIV-1 therapeutics. © 2018 The Author(s).},\r\nfunding_details={National Heart, Lung, and Blood InstituteNIDA},\r\nfunding_details={District of Columbia Developmental Center for AIDS ResearchAI117970},\r\nfunding_details={Российский Фонд Фундаментальных Исследований (РФФИ)12-04-91444-NIZ},\r\nfunding_details={NIH Blueprint for Neuroscience Research1R01HL125005, U19AI109664, P30AI117970, 1P50HL118006, 1UM1AI26617, 5G12MD007597},\r\nfunding_details={Ministry of Education and Science of the Russian Federation2012-1.5-12-000-1001-030},\r\n}","author_short":["Ivanov, A.","Lin, X.","Ammosova, T.","Ilatovskiy, A.","Kumari, N.","Lassiter, H.","Afangbedji, N.","Niu, X.","Petukhov, M.","Nekhai, S."],"key":"Ivanov2018","id":"Ivanov2018","bibbaseid":"ivanov-lin-ammosova-ilatovskiy-kumari-lassiter-afangbedji-niu-etal-hiv1tatphosphorylationonser16residuemodulateshiv1transcription-2018","role":"author","urls":{"Paper":"https://www.scopus.com/inward/record.uri?eid=2-s2.0-85047482579&doi=10.1186%2fs12977-018-0422-5&partnerID=40&md5=80ac4eaa0e53385e032d2c6db96a912e"},"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://bio.pnpi.nrcki.ru/wp-content/uploads/2019/12/lbm_2019_10.txt","dataSources":["YYLjupmCazkNqWNEJ"],"keywords":[],"search_terms":["hiv","tat","phosphorylation","ser","residue","modulates","hiv","transcription","ivanov","lin","ammosova","ilatovskiy","kumari","lassiter","afangbedji","niu","petukhov","nekhai"],"title":"HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription","year":2018}