: / RNA polymerase II CTD heptapeptide repeat S5 kinase activity / cyclin A2-CDK1 complex / cell cycle G1/S phase transition / ventricular system development / cellular response to luteinizing hormone stimulus / snRNA transcription by RNA polymerase II / CAK-ERCC2 complex / transcription factor TFIIK complex / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 ...: / RNA polymerase II CTD heptapeptide repeat S5 kinase activity / cyclin A2-CDK1 complex / cell cycle G1/S phase transition / ventricular system development / cellular response to luteinizing hormone stimulus / snRNA transcription by RNA polymerase II / CAK-ERCC2 complex / transcription factor TFIIK complex / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / cellular response to leptin stimulus / adult heart development / transcription factor TFIIH core complex / transcription factor TFIIH holo complex / male pronucleus / cyclin-dependent protein serine/threonine kinase activator activity / female pronucleus / cellular response to cocaine / [RNA-polymerase]-subunit kinase / response to glucagon / RNA Polymerase I Transcription Termination / positive regulation of DNA biosynthetic process / cyclin-dependent protein serine/threonine kinase regulator activity / cellular response to insulin-like growth factor stimulus / cyclin A1-CDK2 complex / cyclin E2-CDK2 complex / cyclin E1-CDK2 complex / cyclin A2-CDK2 complex / positive regulation of DNA-templated DNA replication initiation / G2 Phase / Y chromosome / cyclin-dependent protein kinase activity / Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes / RNA Pol II CTD phosphorylation and interaction with CE during HIV infection / RNA Pol II CTD phosphorylation and interaction with CE / positive regulation of heterochromatin formation / p53-Dependent G1 DNA Damage Response / 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 / Formation of the Early Elongation Complex / Formation of the HIV-1 Early Elongation Complex / X chromosome / mRNA Capping / PTK6 Regulates Cell Cycle / regulation of anaphase-promoting complex-dependent catabolic process / Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) / centriole replication / Regulation of APC/C activators between G1/S and early anaphase / regulation of DNA replication / telomere maintenance in response to DNA damage / microtubule organizing center / centrosome duplication / RNA Polymerase I Transcription Initiation / regulation of G1/S transition of mitotic cell cycle / G0 and Early G1 / cochlea development / RNA polymerase II transcribes snRNA genes / Telomere Extension By Telomerase / animal organ regeneration / Activation of the pre-replicative complex / cyclin-dependent kinase / ATP-dependent activity, acting on DNA / cyclin-dependent protein serine/threonine kinase activity / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / Activation of ATR in response to replication stress / Regulation of MITF-M-dependent genes involved in cell cycle and proliferation / Cajal body / Cyclin E associated events during G1/S transition / Formation of HIV elongation complex in the absence of HIV Tat / Cyclin A:Cdk2-associated events at S phase entry / Cyclin A/B1/B2 associated events during G2/M transition / cyclin-dependent protein kinase holoenzyme complex / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / condensed chromosome / regulation of G2/M transition of mitotic cell cycle / cellular response to platelet-derived growth factor stimulus / mitotic G1 DNA damage checkpoint signaling / RNA Polymerase II Pre-transcription Events / positive regulation of smooth muscle cell proliferation / RNA polymerase II CTD heptapeptide repeat kinase activity / cellular response to nitric oxide / post-translational protein modification / regulation of mitotic cell cycle / cyclin binding / positive regulation of DNA replication / meiotic cell cycle / male germ cell nucleus / nucleotide-excision repair / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / RNA Polymerase I Promoter Escape 類似検索 - 分子機能
CyclinH/Ccl1 / Cyclin-dependent kinase 7 / Cdk-activating kinase assembly factor MAT1/Tfb3 / Cdk-activating kinase assembly factor MAT1, centre / CDK-activating kinase assembly factor MAT1 / Zinc finger, C3HC4 type (RING finger) / Cyclin-A, N-terminal APC/C binding region / Cyclin-A N-terminal APC/C binding region / Cyclin, C-terminal domain 2 / Cyclin C-terminal domain ...CyclinH/Ccl1 / Cyclin-dependent kinase 7 / Cdk-activating kinase assembly factor MAT1/Tfb3 / Cdk-activating kinase assembly factor MAT1, centre / CDK-activating kinase assembly factor MAT1 / Zinc finger, C3HC4 type (RING finger) / Cyclin-A, N-terminal APC/C binding region / Cyclin-A N-terminal APC/C binding region / Cyclin, C-terminal domain 2 / Cyclin C-terminal domain / : / Cyclin, C-terminal domain / : / Cyclins signature. / Cyclin / Cyclin/Cyclin-like subunit Ssn8 / Cyclin, C-terminal domain / Cyclin_C / Ubiquitin interacting motif / Ubiquitin-interacting motif (UIM) domain profile. / Cyclin, N-terminal / Cyclin, N-terminal domain / Cyclin-like / domain present in cyclins, TFIIB and Retinoblastoma / Cyclin-like superfamily / : / Zinc finger, RING-type, conserved site / Zinc finger RING-type signature. / Ring finger / Zinc finger RING-type profile. / Zinc finger, RING-type / Zinc finger, RING/FYVE/PHD-type / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性
ジャーナル: Science / 年: 2025 タイトル: Structural basis of T-loop-independent recognition and activation of CDKs by the CDK-activating kinase. 著者: Victoria I Cushing / Amy J S McGeoch / Sophie L Williams / Theodoros I Roumeliotis / Junjie Feng / Lucy M Dan / Jyoti S Choudhary / Norman E Davey / Basil J Greber / 要旨: Cyclin-dependent kinases (CDKs) are prototypical regulators of the cell cycle. The CDK-activating kinase (CAK) acts as a master regulator of CDK activity by catalyzing the activating phosphorylation ...Cyclin-dependent kinases (CDKs) are prototypical regulators of the cell cycle. The CDK-activating kinase (CAK) acts as a master regulator of CDK activity by catalyzing the activating phosphorylation of CDKs on a conserved threonine residue within the regulatory T-loop. However, structural data illuminating the mechanism by which the CAK recognizes and activates CDKs have remained elusive. In this study, we determined high-resolution structures of the CAK in complex with CDK2 and CDK2-cyclin A2 by cryogenic electron microscopy. Our structures reveal a T-loop-independent kinase-kinase interface with contributions from both kinase lobes. Computational analysis and structures of the CAK in complex with CDK1-cyclin B1 and CDK11 indicate that these structures represent the general architecture of CAK-CDK complexes. These results advance our mechanistic understanding of cell cycle regulation and kinase signaling cascades.