ArticleProceedings of the National Academy of Sciences of the United States of America1999
Specific interaction of Tat with the human but not rodent P-TEFb complex mediates the species-specific Tat activation of HIV-1 transcription.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 59 citations in OpenAlex.
- The HIV-1 Transcriptional Program: From Initiation to Elongation Control.Journal of molecular biology · 2025Review
- Brd4 and HEXIM1: multiple roles in P-TEFb regulation and cancer.BioMed research international · 2014Review
- Transition step during assembly of HIV Tat:P-TEFb transcription complexes and transfer to TAR RNA.Molecular and cellular biology · 2012Article
- Recruitment of TFIIH to the HIV LTR is a rate-limiting step in the emergence of HIV from latency.The EMBO journal · 2006Article
- Effect of SWI/SNF chromatin remodeling complex on HIV-1 Tat activated transcription.Retrovirology · 2006Article
- Arginine methylation regulates IL-2 gene expression: a role for protein arginine methyltransferase 5 (PRMT5).The Biochemical journal · 2005Article
- Selection of TAR RNA-binding chameleon peptides by using a retroviral replication system.Journal of virology · 2004Article
- Replication of human immunodeficiency viruses engineered with heterologous Tat-transactivation response element interactions.Journal of virology · 2003Article
- HIV-1 Tat targets microtubules to induce apoptosis, a process promoted by the pro-apoptotic Bcl-2 relative Bim.The EMBO journal · 2002Article
- Differential acetylation of Tat coordinates its interaction with the co-activators cyclin T1 and PCAF.The EMBO journal · 2002Article
- RNA interference directed against viral and cellular targets inhibits human immunodeficiency Virus Type 1 replication.Journal of virology · 2002Article
- A minimal chimera of human cyclin T1 and tat binds TAR and activates human immunodeficiency virus transcription in murine cells.Journal of virology · 2002Article
- Phosphorylation of the RNA polymerase II carboxyl-terminal domain by CDK9 is directly responsible for human immunodeficiency virus type 1 Tat-activated transcriptional elongation.Molecular and cellular biology · 2002Article
- TAR RNA loop: a scaffold for the assembly of a regulatory switch in HIV replication.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- Spt5 cooperates with human immunodeficiency virus type 1 Tat by preventing premature RNA release at terminator sequences.Molecular and cellular biology · 2002Article
- CDK9 autophosphorylation regulates high-affinity binding of the human immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA.Molecular and cellular biology · 2000Article
- Relief of two built-In autoinhibitory mechanisms in P-TEFb is required for assembly of a multicomponent transcription elongation complex at the human immunodeficiency virus type 1 promoter.Molecular and cellular biology · 2000Article
- Domains in the SPT5 protein that modulate its transcriptional regulatory properties.Molecular and cellular biology · 2000Article
- Tat-SF1 protein associates with RAP30 and human SPT5 proteins.Molecular and cellular biology · 1999Article
- Tat activates human immunodeficiency virus type 1 transcriptional elongation independent of TFIIH kinase.Molecular and cellular biology · 1999Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Tat stimulation of HIV-1 transcriptional elongation is species-specific and is believed to require a specific cellular cofactor present in many human and primate cells but not in nonpermissive rodent cells. Human P-TEFb, composed of Cdk9 and cyclin T1, is a general transcription elongation factor that phosphorylates the C-terminal domain of RNA polymerase II. Previous studies have also implicated P-TEFb as a Tat-specific cellular cofactor and, in particular, human cyclin T1 as responsible for the species-specific Tat activation. To obtain functional evidence in support of these hypotheses, we generated and examined the activities of human-rodent "hybrid" P-TEFb complexes. We found that P-TEFb complexes containing human cyclin T1 complexed with either human or rodent Cdk9 supported Tat transactivation and interacted with the Tat activation domain and the HIV-1 TAR RNA element to form TAR loop-dependent ribonucleoprotein complexes. Although a stable complex containing rodent cyclin T1 and human Cdk9 was capable of phosphorylating CTD and mediating basal HIV-1 elongation, it failed to interact with Tat and to mediate Tat transactivation, indicating that the abilities of P-TEFb to support basal elongation and Tat activation can be separated. Together, our data indicated that the specific interaction of human P-TEFb with Tat/TAR, mostly through cyclin T1, is crucial for P-TEFb to mediate a Tat-specific and species-restricted activation of HIV-1 transcription. Amino acid residues unique to human Cdk9 also contributed partially to the formation of the P-TEFb-Tat-TAR complex. Moreover, the cyclin box of cyclin T1 and its immediate flanking region are largely responsible for the specific P-TEFb-Tat interaction.
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