PITALRE, the Catalytic Subunit of TAK, is Required for Human Immunodeficiency Virus Tat Transactivation in Vivo

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1998 Apr 29

PMID 9557739

Citations 54

Authors

M O Gold

X Yang

C H Herrmann

A.P. Rice

Affiliations

Soon will be listed here.

Abstract

The human cdc2-related kinase PITALRE is the catalytic component of TAK, the Tat-associated kinase. Previously, we have proposed that TAK is a cellular factor that mediates Tat transactivation function. Here we demonstrate that transient overexpression of PITALRE specifically squelches Tat-1 activation of both a transfected and an integrated human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR), suggesting that PITALRE mediates Tat function as a multiprotein complex. A catalytic mutant of PITALRE, D167N, was found to be more efficient than wild-type PITALRE in squelching Tat transactivation. Neither wild-type PITALRE nor D167N was able to squelch transactivation of the human T-cell leukemia type 1 LTR by the Tax protein. Additionally, we show that artificial targeting of PITALRE to a nascent RNA element, in the absence of Tat, activated HIV-1 LTR expression. These results indicate that a PITALRE-containing complex mediates transactivation by Tat and suggest that Tat proteins function by localizing such a PITALRE-containing complex to the site of the transcribing provirus.

Citing Articles

LDC000067, a CDK9 inhibitor, unveils promising results in suppressing influenza virus infections and .

Zhang M, Lian X, Gao Y, Jiang L, Li Z, Zhang H Antimicrob Agents Chemother. 2024; 69(1):e0117224.

PMID: 39565117 PMC: 11784216. DOI: 10.1128/aac.01172-24.

Help or Hinder: Protein Host Factors That Impact HIV-1 Replication.

Moezpoor M, Stevenson M Viruses. 2024; 16(8).

PMID: 39205255 PMC: 11360189. DOI: 10.3390/v16081281.

The cell biology of HIV-1 latency and rebound.

Mbonye U, Karn J Retrovirology. 2024; 21(1):6.

PMID: 38580979 PMC: 10996279. DOI: 10.1186/s12977-024-00639-w.

Identification of a novel CDK9 inhibitor targeting the intramolecular hidden cavity of CDK9 induced by Tat binding.

Asamitsu K, Hirokawa T, Okamoto T PLoS One. 2022; 17(11):e0277024.

PMID: 36378653 PMC: 9665388. DOI: 10.1371/journal.pone.0277024.

Nuclear Transit and HIV LTR Binding of NF-κB Subunits Held by IκB Proteins: Implications for HIV-1 Activation.

Khan S, Gasperino S, Zeichner S Viruses. 2020; 11(12).

PMID: 31888181 PMC: 6949894. DOI: 10.3390/v11121162.

References

OBrien T, Hardin S, Greenleaf A, Lis J . Phosphorylation of RNA polymerase II C-terminal domain and transcriptional elongation. Nature. 1994; 370(6484):75-7. DOI: 10.1038/370075a0. View

Grana X, De Luca A, Sang N, Fu Y, Claudio P, Rosenblatt J . PITALRE, a nuclear CDC2-related protein kinase that phosphorylates the retinoblastoma protein in vitro. Proc Natl Acad Sci U S A. 1994; 91(9):3834-8. PMC: 43676. DOI: 10.1073/pnas.91.9.3834. View

Rhim H, Rice A . Exon2 of HIV-2 Tat contributes to transactivation of the HIV-2 LTR by increasing binding affinity to HIV-2 TAR RNA. Nucleic Acids Res. 1994; 22(21):4405-13. PMC: 308473. DOI: 10.1093/nar/22.21.4405. View

Jones K, Peterlin B . Control of RNA initiation and elongation at the HIV-1 promoter. Annu Rev Biochem. 1994; 63:717-43. DOI: 10.1146/annurev.bi.63.070194.003441. View

Zhou Q, Sharp P . Novel mechanism and factor for regulation by HIV-1 Tat. EMBO J. 1995; 14(2):321-8. PMC: 398086. DOI: 10.1002/j.1460-2075.1995.tb07006.x. View

Herrmann C, Rice A . Lentivirus Tat proteins specifically associate with a cellular protein kinase, TAK, that hyperphosphorylates the carboxyl-terminal domain of the large subunit of RNA polymerase II: candidate for a Tat cofactor. J Virol. 1995; 69(3):1612-20. PMC: 188757. DOI: 10.1128/JVI.69.3.1612-1620.1995. View

Madore S, Cullen B . Functional similarities between HIV-1 Tat and DNA sequence-specific transcriptional activators. Virology. 1995; 206(2):1150-4. DOI: 10.1006/viro.1995.1041. View

Liao S, Zhang J, Jeffery D, Koleske A, Thompson C, Chao D . A kinase-cyclin pair in the RNA polymerase II holoenzyme. Nature. 1995; 374(6518):193-6. DOI: 10.1038/374193a0. View

Sune C, Garcia-Blanco M . Transcriptional trans activation by human immunodeficiency virus type 1 Tat requires specific coactivators that are not basal factors. J Virol. 1995; 69(5):3098-107. PMC: 189011. DOI: 10.1128/JVI.69.5.3098-3107.1995. View

10.

Kuchin S, Yeghiayan P, Carlson M . Cyclin-dependent protein kinase and cyclin homologs SSN3 and SSN8 contribute to transcriptional control in yeast. Proc Natl Acad Sci U S A. 1995; 92(9):4006-10. PMC: 42091. DOI: 10.1073/pnas.92.9.4006. View

11.

Wahi M, Johnson A . Identification of genes required for alpha 2 repression in Saccharomyces cerevisiae. Genetics. 1995; 140(1):79-90. PMC: 1206574. DOI: 10.1093/genetics/140.1.79. View

12.

Yankulov K, Yamashita K, Roy R, Egly J, Bentley D . The transcriptional elongation inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole inhibits transcription factor IIH-associated protein kinase. J Biol Chem. 1995; 270(41):23922-5. DOI: 10.1074/jbc.270.41.23922. View

13.

Maldonado E, Shiekhattar R, Sheldon M, Cho H, Drapkin R, Rickert P . A human RNA polymerase II complex associated with SRB and DNA-repair proteins. Nature. 1996; 381(6577):86-9. DOI: 10.1038/381086a0. View

14.

Yang X, Herrmann C, Rice A . The human immunodeficiency virus Tat proteins specifically associate with TAK in vivo and require the carboxyl-terminal domain of RNA polymerase II for function. J Virol. 1996; 70(7):4576-84. PMC: 190394. DOI: 10.1128/JVI.70.7.4576-4584.1996. View

15.

Fraser N, Sehgal P, Darnell J . DRB-induced premature termination of late adenovirus transcription. Nature. 1978; 272(5654):590-3. DOI: 10.1038/272590a0. View

16.

Tamm I, Kikuchi T . Early termination of heterogeneous nuclear RNA transcripts in mammalian cells: accentuation by 5,6-dichloro 1-beta-D-ribofuranosylbenzimidazole. Proc Natl Acad Sci U S A. 1979; 76(11):5750-4. PMC: 411728. DOI: 10.1073/pnas.76.11.5750. View

17.

Sodroski J, Patarca R, Rosen C, Wong-Staal F, Haseltine W . Location of the trans-activating region on the genome of human T-cell lymphotropic virus type III. Science. 1985; 229(4708):74-7. DOI: 10.1126/science.2990041. View

18.

Zandomeni R, Zandomeni M, SHUGAR D, Weinmann R . Casein kinase type II is involved in the inhibition by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole of specific RNA polymerase II transcription. J Biol Chem. 1986; 261(7):3414-9. View

19.

Dayton A, Sodroski J, Rosen C, Goh W, Haseltine W . The trans-activator gene of the human T cell lymphotropic virus type III is required for replication. Cell. 1986; 44(6):941-7. DOI: 10.1016/0092-8674(86)90017-6. View

20.

Fisher A, Feinberg M, Josephs S, Harper M, Marselle L, Reyes G . The trans-activator gene of HTLV-III is essential for virus replication. Nature. 1986; 320(6060):367-71. DOI: 10.1038/320367a0. View