LRR domain binding / microfibril binding / RNA Polymerase III Chain Elongation / RNA Polymerase III Transcription Termination / regulation of transcription by RNA polymerase I / RPAP3/R2TP/prefoldin-like complex / RNA Polymerase III Transcription Initiation From Type 1 Promoter / RNA Polymerase III Transcription Initiation From Type 2 Promoter / RNA Polymerase III Transcription Initiation From Type 3 Promoter / Cytosolic sensors of pathogen-associated DNA ...LRR domain binding / microfibril binding / RNA Polymerase III Chain Elongation / RNA Polymerase III Transcription Termination / regulation of transcription by RNA polymerase I / RPAP3/R2TP/prefoldin-like complex / RNA Polymerase III Transcription Initiation From Type 1 Promoter / RNA Polymerase III Transcription Initiation From Type 2 Promoter / RNA Polymerase III Transcription Initiation From Type 3 Promoter / Cytosolic sensors of pathogen-associated DNA / RNA Polymerase III Abortive And Retractive Initiation / Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / negative regulation of helicase activity / signal transduction by p53 class mediator / negative regulation of G1 to G0 transition / negative regulation of glucose catabolic process to lactate via pyruvate / Transcriptional activation of cell cycle inhibitor p21 / regulation of intrinsic apoptotic signaling pathway by p53 class mediator / negative regulation of pentose-phosphate shunt / ATP-dependent DNA/DNA annealing activity / Activation of NOXA and translocation to mitochondria / regulation of cell cycle G2/M phase transition / regulation of fibroblast apoptotic process / intrinsic apoptotic signaling pathway in response to hypoxia / oligodendrocyte apoptotic process / negative regulation of miRNA processing / positive regulation of thymocyte apoptotic process / oxidative stress-induced premature senescence / regulation of tissue remodeling / glucose catabolic process to lactate via pyruvate / positive regulation of mitochondrial membrane permeability / positive regulation of programmed necrotic cell death / mRNA transcription / bone marrow development / circadian behavior / regulation of mitochondrial membrane permeability involved in apoptotic process / germ cell nucleus / RUNX3 regulates CDKN1A transcription / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / Abortive elongation of HIV-1 transcript in the absence of Tat / TP53 Regulates Transcription of Death Receptors and Ligands / Activation of PUMA and translocation to mitochondria / regulation of DNA damage response, signal transduction by p53 class mediator / FGFR2 alternative splicing / RNA Polymerase I Transcription Termination / histone deacetylase regulator activity / negative regulation of glial cell proliferation / MicroRNA (miRNA) biogenesis / Regulation of TP53 Activity through Association with Co-factors / negative regulation of neuroblast proliferation / Viral Messenger RNA Synthesis / T cell lineage commitment / mitochondrial DNA repair / Signaling by FGFR2 IIIa TM / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / ER overload response / B cell lineage commitment / thymocyte apoptotic process / TP53 Regulates Transcription of Caspase Activators and Caspases / negative regulation of mitophagy / RNA Pol II CTD phosphorylation and interaction with CE during HIV infection / RNA Pol II CTD phosphorylation and interaction with CE / cardiac septum morphogenesis / positive regulation of nuclear-transcribed mRNA poly(A) tail shortening / Formation of the Early Elongation Complex / Formation of the HIV-1 Early Elongation Complex / negative regulation of DNA replication / entrainment of circadian clock by photoperiod / mRNA Capping / HIV Transcription Initiation / RNA Polymerase II HIV Promoter Escape / Transcription of the HIV genome / RNA Polymerase II Promoter Escape / RNA Polymerase II Transcription Pre-Initiation And Promoter Opening / RNA Polymerase II Transcription Initiation / RNA Polymerase II Transcription Initiation And Promoter Clearance / PI5P Regulates TP53 Acetylation / negative regulation of telomere maintenance via telomerase / Zygotic genome activation (ZGA) / positive regulation of release of cytochrome c from mitochondria / Association of TriC/CCT with target proteins during biosynthesis / necroptotic process / mRNA Splicing - Minor Pathway / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / PIWI-interacting RNA (piRNA) biogenesis / TFIID-class transcription factor complex binding / rRNA transcription / SUMOylation of transcription factors / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / maintenance of transcriptional fidelity during transcription elongation by RNA polymerase II / intrinsic apoptotic signaling pathway by p53 class mediator / T cell proliferation involved in immune response / negative regulation of reactive oxygen species metabolic process / RNA Polymerase I Transcription Initiation / nuclear-transcribed mRNA catabolic process / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / positive regulation of execution phase of apoptosis / Processing of Capped Intron-Containing Pre-mRNA 類似検索 - 分子機能
DNA-directed RNA polymerase II subunit RPB4 / Cellular tumor antigen p53 / DNA-directed RNA polymerase II subunit RPB3 / DNA-directed RNA polymerases I, II, and III subunit RPABC1 / DNA-directed RNA polymerase II subunit RPB1 / DNA-directed RNA polymerase II subunit RPB2 / DNA-directed RNA polymerase II subunit RPB9 / DNA-directed RNA polymerases I, II, and III subunit RPABC3 / DNA-directed RNA polymerase II subunit RPB11-a / DNA-directed RNA polymerases I, II, and III subunit RPABC4 ...DNA-directed RNA polymerase II subunit RPB4 / Cellular tumor antigen p53 / DNA-directed RNA polymerase II subunit RPB3 / DNA-directed RNA polymerases I, II, and III subunit RPABC1 / DNA-directed RNA polymerase II subunit RPB1 / DNA-directed RNA polymerase II subunit RPB2 / DNA-directed RNA polymerase II subunit RPB9 / DNA-directed RNA polymerases I, II, and III subunit RPABC3 / DNA-directed RNA polymerase II subunit RPB11-a / DNA-directed RNA polymerases I, II, and III subunit RPABC4 / DNA-directed RNA polymerases I, II, and III subunit RPABC2 / DNA-directed RNA polymerase II subunit RPB7 / DNA-directed RNA polymerases I, II, and III subunit RPABC5 類似検索 - 構成要素
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
1R01GM126045-03
米国
引用
ジャーナル: Commun Biol / 年: 2021 タイトル: Structure of the p53/RNA polymerase II assembly. 著者: Shu-Hao Liou / Sameer K Singh / Robert H Singer / Robert A Coleman / Wei-Li Liu / 要旨: The tumor suppressor p53 protein activates expression of a vast gene network in response to stress stimuli for cellular integrity. The molecular mechanism underlying how p53 targets RNA polymerase II ...The tumor suppressor p53 protein activates expression of a vast gene network in response to stress stimuli for cellular integrity. The molecular mechanism underlying how p53 targets RNA polymerase II (Pol II) to regulate transcription remains unclear. To elucidate the p53/Pol II interaction, we have determined a 4.6 Å resolution structure of the human p53/Pol II assembly via single particle cryo-electron microscopy. Our structure reveals that p53's DNA binding domain targets the upstream DNA binding site within Pol II. This association introduces conformational changes of the Pol II clamp into a further-closed state. A cavity was identified between p53 and Pol II that could possibly host DNA. The transactivation domain of p53 binds the surface of Pol II's jaw that contacts downstream DNA. These findings suggest that p53's functional domains directly regulate DNA binding activity of Pol II to mediate transcription, thereby providing insights into p53-regulated gene expression.
凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK I 詳細: The assembled p53/Pol II co-complex was applied directly on the grid for 10 sec followed by 5.5 sec of blotting. The sample grid was then washed with 3.5% trehalose in 0.1 M KCl/HEM buffer ...詳細: The assembled p53/Pol II co-complex was applied directly on the grid for 10 sec followed by 5.5 sec of blotting. The sample grid was then washed with 3.5% trehalose in 0.1 M KCl/HEM buffer (20 mM HEPES, 0.2 mM EDTA, 2 mM MgCl2 at pH 7.9) for 10 sec, blotted for 5.5 sec, and finally frozen in liquid ethane..
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電子顕微鏡法
顕微鏡
FEI TITAN KRIOS
撮影
フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / 平均露光時間: 0.2 sec. / 平均電子線量: 1.16 e/Å2
電子線
加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN
電子光学系
照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD
実験機器
モデル: Titan Krios / 画像提供: FEI Company
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画像解析
粒子像選択
選択した数: 776710 詳細: 776,710 particles were automatically picked by SPHIRE-crYOLO along with PhosaurusNet network.