Taking a new TAK on Tat transactivation

Jones, Katherine A.

doi:10.1101/gad.11.20.2593

Cited by 202 publications

(161 citation statements)

References 52 publications

(58 reference statements)

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“…T cells are a primary target for HIV infection, and it has been shown that T cell activation induces HIV-1 LTR transcription strongly (Kaufman et al, 1987;Nabel and Baltimore, 1987;Siekevitz et al, 1987;Tong-Starksen et al, 1987). Since the cyclin T1/CDK9 complex is a target of Tat in HIV infected T cells (Figure 2), and Tat activity is essential for HIV replication (Jones, 1997), we sought to ascertain whether activation of cyclin T1 correlates with HIV replication in PBLs. As described above for Figure 6a, PBLs were unstimulated or stimulated with PMA, PHA or PMA and PHA together for 48 h and then infected with HIV-1.…”

Section: Resultsmentioning

confidence: 99%

“…Several of these complexes have been identi®ed hereto with roles in cell cycle regulation and transcription (GranÄ a and Reddy, 1995;Jones, 1997;Morgan, 1997). The activity of cyclin/CDK pairs with roles in cell cycle control is generally regulated by growth factors or is dependent on the cell cycle stage.…”

Section: Introductionmentioning

confidence: 99%

“…Tat pull-down experiments provided early evidence of a Tat-associated kinase (TAK) Rice, 1993, 1995). Tat acts by binding to the nascent transcript containing the TAR sequence and increasing the processivity of RNAP II (Jones, 1997;Jones and Peterlin, 1994). Since the latter function is similar to that of P-TEFb (Marshall et al, 1996;Marshall and Price, 1995) it was not surprising that CDK9 was found to associate with the activation domain of Tat in vitro and in HeLa cells overexpressing Tat (Yang et al, 1997;Zhu et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Upregulation of cyclin T1/CDK9 complexes during T cell activation

et al. 1998

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Cyclin T1 has been identi®ed recently as a regulatory subunit of CDK9 and as a component of the transcription elongation factor P-TEFb. Cyclin T1/CDK9 complexes phosphorylate the carboxy terminal domain (CTD) of RNA polymerase II (RNAP II) in vitro. Here we report that the levels of cyclin T1 are dramatically upregulated by two independent signaling pathways triggered respectively by PMA and PHA in primary human peripheral blood lymphocytes (PBLs). Activation of these two pathways in tandem is su cient for PBLs to enter and progress through the cell cycle. However, the expression of cyclin T1 is not growth and/or cell cycle regulated in other cell types, indicating that regulation of cyclin T1 expression is dependent on tissue-speci®c signaling pathways. Upregulation of cyclin T1 in stimulated PBLs results in induction of the CTD kinase activity of the cyclin T1/CDK9 complex, which in turn correlates directly with phosphorylation of RNAP II in vivo, linking for the ®rst time activation of the cyclin T1/ CDK9 pair with phosphorylation of RNAP II in vivo. In addition, we report here that endogenous CDK9 and cyclin T1 complexes associate with HIV-1 generated Tat in relevant cells and under physiological conditions (HIV-1 infected T cells). This, together with our results showing that HIV-1 replication in stimulated PBLs correlates with the levels of cyclin T1 protein and associated CTD kinase activity, suggests that the cyclin T1/CDK9 pair is one of the HIV-1 required host cellular cofactors generated during T cell activation.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Upregulation of cyclin T1/CDK9 complexes during T cell activation

et al. 1998

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“…It has been shown that Cyclin T binds on its own and in association with CDK9 to the activation domain of Tat and most importantly Cyclin T increases the a nity of Tat for TAR (Wei et al, 1998;Zhou et al, 1998). It has been proposed that Tat upon binding to TAR, recruits the Cyclin T/CDK9 complex leading to hyperphosphorylation of the CTD of RNAPII (Jones, 1997). Thus, recruitment of CyclinT/CDK9 kinase to RNAPII may represent an important rate-limiting step in transcription.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation by targeted recruitment of cyclin-dependent CDK9 kinase in vivo

et al. 1999

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The CDK9 kinase in association with Cyclin T is a component of the transcription positive-acting complex pTEFb which facilitates the transition from abortive to productive transcription elongation by phosphorylating the carboxyl-terminal domain of RNA polymerase II. The Cyclin T1/CDK9 complex is implicated in Tat transactivation, and it has been suggested that Tat functions by recruiting this complex to RNAPII through cooperative binding to RNA. Here, we demonstrate that targeted recruitment of Cyclin T1/CDK9 kinase complex to speci®c promoters, through fusion to a DNA-binding domain of either Cyclin T1 or CDK9 kinase, stimulates transcription in vivo. Transcriptional enhancement was dependent on active CDK9, as a catalytically inactive form had no transcriptional e ect. We determined that, unlike conventional activators, DNA-bound CDK9 does not activate enhancerless TATA-promoters unless TBP is overexpressed, suggesting that CDK9 acts in vivo at a step subsequent to TFIID recruitment DNA-bound. Finally, we determined that CDK9-mediated transcriptional activation is mediated by preferentially stimulating productive transcription elongation.

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“…Tat acts through TAR to control an early step in transcriptional elongation that is sensitive to inhibition by protein kinase inhibitors and requires the CTD of the large subunit of RNA pol II (Jones, 1997). The transactivation domain of Tat interacts strongly with a nuclear Tat-associates kinase, called TAK Rice, 1993, 1995), which was recently shown to be identical to the kinase subunit of P-TEFb (Mancebo et al, 1997;Zhu et al, 1997).…”

Section: Cyclin T and Human Immunodeficiency Virusmentioning

confidence: 99%

Cyclin T: Three forms for different roles in physiological and pathological functions

Luca¹,

Falco

Baldi³

et al. 2002

Journal Cellular Physiology

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Cyclins are members of family of proteins involved in the cell cycle regulation. They are regulatory subunits of complexes with proteins called cyclin-dependent kinases (CDKs). There are three forms of cyclin T: cyclin T1, cyclin T2a, and T2b. All cyclin T contain an N-terminal ''cyclin homology box,'' the most conserved region among different members of the cyclin family that serves to bind CDK9. In addition to the N-terminal cyclin domain, cyclin T contains a putative coiled-coil motif, a His-rich motif, and a C-terminal PEST sequence. The CDK9/cyclin T complex is able to activate gene expression in a catalytic-dependent manner, phosphorylating the carboxy-terminal domain (CTD) of RNA polymerase II. In addition, only cyclin T1 supports interactions between Tat and TAR. The interaction of Tat with cyclin T1 alters the conformation of Tat to enhance the affinity and specificity of the Tat:TAR interaction. On the other hand, CDK9/cyclin T2 complexes are involved in the regulation of terminal differentiation in muscle cells.

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Taking a new TAK on Tat transactivation

Cited by 202 publications

References 52 publications

Upregulation of cyclin T1/CDK9 complexes during T cell activation

Upregulation of cyclin T1/CDK9 complexes during T cell activation

Transcriptional regulation by targeted recruitment of cyclin-dependent CDK9 kinase in vivo

Cyclin T: Three forms for different roles in physiological and pathological functions

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