P-TEFb与RNA聚合酶II的C末端结构域之间的相互作用可激活靶基因上游或下游位点的转录延伸。
Interaction between P-TEFb and the C-terminal domain of RNA polymerase II activates transcriptional elongation from sites upstream or downstream of target genes.
作者信息
Taube Ran, Lin Xin, Irwin Dan, Fujinaga Koh, Peterlin B Matija
机构信息
Howard Hughes Medical Institute, Department of Medicine, University of California at San Francisco, San Francisco, California 94143-0703, USA.
出版信息
Mol Cell Biol. 2002 Jan;22(1):321-31. doi: 10.1128/MCB.22.1.321-331.2002.
Abstract
Transcriptional elongation by RNA polymerase II (RNAPII) is regulated by the positive transcription elongation factor b (P-TEFb). P-TEFb is composed of Cdk9 and C-type cyclin T1 (CycT1), CycT2a, CycT2b, or CycK. The role of the C-terminal region of CycT1 and CycT2 remains unknown. In this report, we demonstrate that these sequences are essential for the activation of transcription by P-TEFb via DNA, i.e., when CycT1 is tethered upstream or downstream of promoters and coding sequences. A histidine-rich stretch, which is conserved between CycT1 and CycT2 in this region, bound the C-terminal domain of RNAPII. This binding was required for the subsequent expression of full-length transcripts from target genes. Thus, P-TEFb could mediate effects of enhancers on the elongation of transcription.
摘要
RNA聚合酶II（RNAPII）的转录延伸受正性转录延伸因子b（P-TEFb）调控。P-TEFb由细胞周期蛋白依赖性激酶9（Cdk9）和C型细胞周期蛋白T1（CycT1）、CycT2a、CycT2b或CycK组成。CycT1和CycT2 C末端区域的作用尚不清楚。在本报告中，我们证明这些序列对于P-TEFb通过DNA激活转录至关重要，即当CycT1锚定在启动子和编码序列的上游或下游时。在该区域CycT1和CycT2之间保守的富含组氨酸的片段与RNAPII的C末端结构域结合。这种结合是随后从靶基因表达全长转录本所必需的。因此，P-TEFb可以介导增强子对转录延伸的作用。
相似文献
1
Interaction between P-TEFb and the C-terminal domain of RNA polymerase II activates transcriptional elongation from sites upstream or downstream of target genes.P-TEFb与RNA聚合酶II的C末端结构域之间的相互作用可激活靶基因上游或下游位点的转录延伸。
Mol Cell Biol. 2002 Jan;22(1):321-31. doi: 10.1128/MCB.22.1.321-331.2002.
2
P-TEFb containing cyclin K and Cdk9 can activate transcription via RNA.包含细胞周期蛋白K和细胞周期蛋白依赖性激酶9的正性转录延伸因子b可通过RNA激活转录。
J Biol Chem. 2002 May 10;277(19):16873-8. doi: 10.1074/jbc.M200117200. Epub 2002 Mar 7.
3
CDK9 autophosphorylation regulates high-affinity binding of the human immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA.细胞周期蛋白依赖性激酶9（CDK9）的自磷酸化调节人类免疫缺陷病毒1型反式激活因子-P-TEFb复合物与反式激活应答元件（TAR）RNA的高亲和力结合。
Mol Cell Biol. 2000 Sep;20(18):6958-69. doi: 10.1128/MCB.20.18.6958-6969.2000.
4
Transcriptional activity and substrate recognition of cyclin T2 from P-TEFb.P-TEFb中细胞周期蛋白T2的转录活性及底物识别
Gene. 2004 Dec 8;343(1):173-9. doi: 10.1016/j.gene.2004.08.027.
5
Human and rodent transcription elongation factor P-TEFb: interactions with human immunodeficiency virus type 1 tat and carboxy-terminal domain substrate.人类和啮齿动物转录延伸因子P-TEFb：与1型人类免疫缺陷病毒tat及羧基末端结构域底物的相互作用
J Virol. 1999 Jul;73(7):5448-58. doi: 10.1128/JVI.73.7.5448-5458.1999.
6
Recruitment of cyclin T1/P-TEFb to an HIV type 1 long terminal repeat promoter proximal RNA target is both necessary and sufficient for full activation of transcription.细胞周期蛋白T1/正性转录延伸因子b（P-TEFb）被招募至HIV-1长末端重复序列启动子近端RNA靶点，这对于转录的完全激活而言，既是必要的，也是充分的。
Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7791-6. doi: 10.1073/pnas.96.14.7791.
7
The growth factor granulin interacts with cyclin T1 and modulates P-TEFb-dependent transcription.生长因子颗粒蛋白与细胞周期蛋白T1相互作用并调节P-TEFb依赖性转录。
Mol Cell Biol. 2003 Mar;23(5):1688-702. doi: 10.1128/MCB.23.5.1688-1702.2003.
8
A model of repression: CTD analogs and PIE-1 inhibit transcriptional elongation by P-TEFb.一种抑制模型：CTD类似物和PIE-1抑制P-TEFb介导的转录延伸。
Genes Dev. 2003 Mar 15;17(6):748-58. doi: 10.1101/gad.1068203.
9
Requirement for a kinase-specific chaperone pathway in the production of a Cdk9/cyclin T1 heterodimer responsible for P-TEFb-mediated tat stimulation of HIV-1 transcription.在产生负责P-TEFb介导的HIV-1转录的tat刺激的Cdk9/细胞周期蛋白T1异二聚体过程中对激酶特异性伴侣蛋白途径的需求。
J Biol Chem. 2000 Jan 7;275(1):279-87. doi: 10.1074/jbc.275.1.279.
10
Transient induction of cyclin T1 during human macrophage differentiation regulates human immunodeficiency virus type 1 Tat transactivation function.人巨噬细胞分化过程中细胞周期蛋白T1的瞬时诱导调节1型人类免疫缺陷病毒Tat反式激活功能。
J Virol. 2002 Nov;76(21):10579-87. doi: 10.1128/jvi.76.21.10579-10587.2002.
引用本文的文献
1
The general transcription factors (GTFs) of RNA polymerase II and their roles in plant development and stress responses.RNA 聚合酶 II 的一般转录因子及其在植物发育和应激反应中的作用。
Crit Rev Biochem Mol Biol. 2024 Oct;59(5):267-309. doi: 10.1080/10409238.2024.2408562. Epub 2024 Oct 3.
2
P-TEFb: The master regulator of transcription elongation.P-TEFb：转录延伸的主控调节因子。
Mol Cell. 2023 Feb 2;83(3):393-403. doi: 10.1016/j.molcel.2022.12.006. Epub 2023 Jan 3.
3
Identification of Novel Nucleocapsid Chimeric Proteins Inhibiting HIV-1 Replication.鉴定新型核衣壳嵌合蛋白抑制 HIV-1 复制。
Int J Mol Sci. 2022 Oct 15;23(20):12340. doi: 10.3390/ijms232012340.
4
Reversible phosphorylation of cyclin T1 promotes assembly and stability of P-TEFb.细胞周期蛋白 T1 的可逆磷酸化促进 P-TEFb 的组装和稳定。
Elife. 2021 Nov 25;10:e68473. doi: 10.7554/eLife.68473.
5
CDK9 keeps RNA polymerase II on track.CDK9 使 RNA 聚合酶 II 保持在轨道上。
Cell Mol Life Sci. 2021 Jul;78(14):5543-5567. doi: 10.1007/s00018-021-03878-8. Epub 2021 Jun 19.
6
CDK9: A Comprehensive Review of Its Biology, and Its Role as a Potential Target for Anti-Cancer Agents.细胞周期蛋白依赖性激酶9：对其生物学特性及其作为抗癌药物潜在靶点作用的全面综述
Front Oncol. 2021 May 10;11:678559. doi: 10.3389/fonc.2021.678559. eCollection 2021.
7
Live-cell imaging reveals the spatiotemporal organization of endogenous RNA polymerase II phosphorylation at a single gene.活细胞成像揭示了内源性 RNA 聚合酶 II 磷酸化在单个基因上的时空组织。
Nat Commun. 2021 May 26;12(1):3158. doi: 10.1038/s41467-021-23417-0.
8
P-TEFb as A Promising Therapeutic Target.P-TEFb 作为一种有前途的治疗靶点。
Molecules. 2020 Feb 14;25(4):838. doi: 10.3390/molecules25040838.
9
BRD4 inhibitor and histone deacetylase inhibitor synergistically inhibit the proliferation of gallbladder cancer in vitro and in vivo.BRD4 抑制剂和组蛋白去乙酰化酶抑制剂协同抑制胆囊癌细胞在体外和体内的增殖。
Cancer Sci. 2019 Aug;110(8):2493-2506. doi: 10.1111/cas.14102. Epub 2019 Jul 11.
10
Targeting transcriptional machinery to inhibit enhancer-driven gene expression in heart failure.靶向转录机制抑制心力衰竭中增强子驱动的基因表达。
Heart Fail Rev. 2019 Sep;24(5):725-741. doi: 10.1007/s10741-019-09792-3.
本文引用的文献
1
NF-kappaB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II.核因子κB结合正性转录延伸因子b以刺激RNA聚合酶II的转录延伸。
Mol Cell. 2001 Aug;8(2):327-37. doi: 10.1016/s1097-2765(01)00314-8.
2
Androgen receptor interacts with the positive elongation factor P-TEFb and enhances the efficiency of transcriptional elongation.雄激素受体与正向延伸因子P-TEFb相互作用，并提高转录延伸效率。
J Biol Chem. 2001 Mar 30;276(13):9978-84. doi: 10.1074/jbc.M002285200. Epub 2000 Dec 21.
3
Positive transcription elongation factor B phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase.正性转录延伸因子B独立于细胞周期蛋白依赖性激酶激活激酶对hSPT5和RNA聚合酶II羧基末端结构域进行磷酸化。
J Biol Chem. 2001 Apr 13;276(15):12317-23. doi: 10.1074/jbc.M010908200. Epub 2001 Jan 5.
4
DSIF and NELF interact with RNA polymerase II elongation complex and HIV-1 Tat stimulates P-TEFb-mediated phosphorylation of RNA polymerase II and DSIF during transcription elongation.DSIF和NELF与RNA聚合酶II延伸复合物相互作用，并且在转录延伸过程中，HIV-1反式激活因子（Tat）刺激P-TEFb介导的RNA聚合酶II和DSIF的磷酸化。
J Biol Chem. 2001 Apr 20;276(16):12951-8. doi: 10.1074/jbc.M006130200. Epub 2000 Dec 8.
5
Orchestrated response: a symphony of transcription factors for gene control.精心编排的应答：用于基因调控的转录因子交响曲。
Genes Dev. 2000 Oct 15;14(20):2551-69. doi: 10.1101/gad.831000.
6
Transcriptional activity of positive transcription elongation factor b kinase in vivo requires the C-terminal domain of RNA polymerase II.体内正转录延伸因子b激酶的转录活性需要RNA聚合酶II的C末端结构域。
Gene. 2000 Aug 22;254(1-2):139-45. doi: 10.1016/s0378-1119(00)00278-x.
7
CDK9 autophosphorylation regulates high-affinity binding of the human immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA.细胞周期蛋白依赖性激酶9（CDK9）的自磷酸化调节人类免疫缺陷病毒1型反式激活因子-P-TEFb复合物与反式激活应答元件（TAR）RNA的高亲和力结合。
Mol Cell Biol. 2000 Sep;20(18):6958-69. doi: 10.1128/MCB.20.18.6958-6969.2000.
8
Control of elongation by RNA polymerase II.RNA聚合酶II对延伸的调控。
Trends Biochem Sci. 2000 Aug;25(8):375-80. doi: 10.1016/s0968-0004(00)01615-7.
9
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.在人免疫缺陷病毒1型启动子处组装多组分转录延伸复合物需要解除P-TEFb中的两种内在自抑制机制。
Mol Cell Biol. 2000 Aug;20(16):5897-907. doi: 10.1128/MCB.20.16.5897-5907.2000.
10
Conditional expression of RNA polymerase II in mammalian cells. Deletion of the carboxyl-terminal domain of the large subunit affects early steps in transcription.RNA聚合酶II在哺乳动物细胞中的条件性表达。大亚基羧基末端结构域的缺失影响转录的早期步骤。
J Biol Chem. 2000 Aug 11;275(32):24375-82. doi: 10.1074/jbc.M001883200.
Zotero 插件