CDK9: a signaling hub for transcriptional control.

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Transcription-Austin Pub Date : 2019-04-01 Epub Date: 2018-10-11 DOI:10.1080/21541264.2018.1523668
Curtis W Bacon, Iván D'Orso
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引用次数: 115

Abstract

Cyclin-dependent kinase 9 (CDK9) is critical for RNA Polymerase II (Pol II) transcription initiation, elongation, and termination in several key biological processes including development, differentiation, and cell fate responses. A broad range of diseases are characterized by CDK9 malfunction, illustrating its importance in maintaining transcriptional homeostasis in basal- and signal-regulated conditions. Here we provide a historical recount of CDK9 discovery and the current models suggesting CDK9 is a central hub necessary for proper execution of different steps in the transcription cycle. Finally, we discuss the current therapeutic strategies to treat CDK9 malfunction in several disease states. Abbreviations: CDK: Cyclin-dependent kinase; Pol II: RNA Polymerase II; PIC: Pre-initiation Complex; TFIIH: Transcription Factor-II H; snoRNA: small nucleolar RNA; CycT: CyclinT1/T2; P-TEFb: Positive Transcription Elongation Factor Complex; snRNP: small nuclear ribonucleo-protein; HEXIM: Hexamethylene Bis-acetamide-inducible Protein 1/2; LARP7: La-related Protein 7; MePCE: Methylphosphate Capping Enzyme; HIV: human immunodeficiency virus; TAT: trans-activator of transcription; TAR: Trans-activation response element; Hsp70: Heat Shock Protein 70; Hsp90/Cdc37: Hsp90- Hsp90 co-chaperone Cdc37; DSIF: DRB Sensitivity Inducing Factor; NELF: Negative Elongation Factor; CPSF: cleavage and polyadenylation-specific factor; CSTF: cleavage-stimulatory factor; eRNA: enhancer RNA; BRD4: Bromodomain-containing protein 4; JMJD6: Jumonji C-domain-containing protein 6; SEC: Super Elongation Complex; ELL: eleven-nineteen Lys-rich leukemia; ENL: eleven-nineteen leukemia; MLL: mixed lineage leukemia; BEC: BRD4-containing Elongation Complex; SEC-L2/L3: SEC-like complexes; KAP1: Kruppel-associated box-protein 1; KEC: KAP1-7SK Elongation Complex; DRB: Dichloro-1-ß-D-Ribofuranosylbenzimidazole; H2Bub1: H2B mono-ubiquitination; KM: KM05382; PP1: Protein Phosphatase 1; CDK9i: CDK9 inhibitor; SHAPE: Selective 2'-hydroxyl acylation analyzed by primer extension; TE: Typical enhancer; SE : Super enhancer.

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CDK9:转录控制的信号中枢。
细胞周期蛋白依赖性激酶9 (CDK9)是RNA聚合酶II (Pol II)转录起始、延伸和终止几个关键生物学过程的关键,包括发育、分化和细胞命运反应。许多疾病都以CDK9功能障碍为特征,这说明了它在基础和信号调节条件下维持转录稳态的重要性。在这里,我们提供了CDK9发现的历史叙述和当前的模型,表明CDK9是转录周期中正确执行不同步骤所必需的中心枢纽。最后,我们讨论了目前治疗几种疾病状态下CDK9功能障碍的治疗策略。CDK:细胞周期蛋白依赖性激酶;RNA聚合酶II;PIC:预起始配合物;TFIIH:转录因子;snoRNA:小核仁RNA;CycT: CyclinT1 / T2;P-TEFb:正转录延伸因子复合体;snRNP:小核糖核蛋白;HEXIM:六亚甲基双乙酰酰胺诱导蛋白1/2;LARP7: la相关蛋白7;甲基磷酸盖帽酶;艾滋病毒:人类免疫缺陷病毒;TAT:转录反式激活因子;TAR:反式激活反应元件;Hsp70:热休克蛋白70;Hsp90/Cdc37: Hsp90- Hsp90共伴蛋白Cdc37;DSIF: DRB敏感诱导因子;负伸长系数;CPSF:裂解和聚腺苷化特异性因子;促卵裂因子;eRNA:增强子RNA;BRD4:含溴结构域蛋白4;JMJD6:巨蒙基含c结构域蛋白6;SEC:超延伸配合物;ELL: 119lyys -rich白血病;ENL: 11 - 19白血病;混合系白血病;BEC:含brd4延伸络合物;SEC-L2/L3: sec样配合物;KAP1: Kruppel-associated box protein 1;KEC: KAP1-7SK延伸配合物;DRB: Dichloro-1 -ß-D-Ribofuranosylbenzimidazole;H2Bub1: H2B单泛素化;公里:KM05382;PP1:蛋白磷酸酶1;CDK9i: CDK9抑制剂;SHAPE:引物延伸分析选择性2'-羟基酰化;TE:典型增强器;SE:超级增强剂。
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来源期刊
Transcription-Austin
Transcription-Austin BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
6.50
自引率
5.60%
发文量
9
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