regulation of Schwann cell differentiation / cyclin A1-CDK1 complex / regulation of attachment of mitotic spindle microtubules to kinetochore / pronuclear fusion / response to DDT / cyclin B1-CDK1 complex / positive regulation of mitochondrial ATP synthesis coupled electron transport / regulation of chromosome condensation / Mitotic Prophase / positive regulation of mitotic sister chromatid segregation ...regulation of Schwann cell differentiation / cyclin A1-CDK1 complex / regulation of attachment of mitotic spindle microtubules to kinetochore / pronuclear fusion / response to DDT / cyclin B1-CDK1 complex / positive regulation of mitochondrial ATP synthesis coupled electron transport / regulation of chromosome condensation / Mitotic Prophase / positive regulation of mitotic sister chromatid segregation / histone kinase activity / Golgi disassembly / E2F-enabled inhibition of pre-replication complex formation / G2/M DNA replication checkpoint / microtubule cytoskeleton organization involved in mitosis / ventricular cardiac muscle cell development / Depolymerization of the Nuclear Lamina / MASTL Facilitates Mitotic Progression / positive regulation of mRNA 3'-end processing / regulation of mitotic cell cycle spindle assembly checkpoint / positive regulation of attachment of spindle microtubules to kinetochore / Activation of NIMA Kinases NEK9, NEK6, NEK7 / mitotic nuclear membrane disassembly / : / patched binding / RNA polymerase II CTD heptapeptide repeat S5 kinase activity / cyclin A2-CDK1 complex / Phosphorylation of Emi1 / Transcriptional regulation by RUNX2 / ventricular system development / tissue regeneration / Phosphorylation of the APC/C / Nuclear Pore Complex (NPC) Disassembly / snRNA transcription by RNA polymerase II / CAK-ERCC2 complex / transcription factor TFIIK complex / outer kinetochore / protein localization to kinetochore / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / adult heart development / Initiation of Nuclear Envelope (NE) Reformation / Polo-like kinase mediated events / transcription factor TFIIH core complex / transcription factor TFIIH holo complex / cellular response to fatty acid / Golgi Cisternae Pericentriolar Stack Reorganization / cyclin-dependent protein serine/threonine kinase activator activity / Condensation of Prometaphase Chromosomes / chromosome condensation / digestive tract development / oocyte maturation / [RNA-polymerase]-subunit kinase / centrosome cycle / RNA Polymerase I Transcription Termination / cyclin-dependent protein serine/threonine kinase regulator activity / response to copper ion / mitotic metaphase chromosome alignment / MAPK3 (ERK1) activation / response to amine / cyclin-dependent protein kinase activity / RNA Pol II CTD phosphorylation and interaction with CE during HIV infection / RNA Pol II CTD phosphorylation and interaction with CE / 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 / G1/S-Specific Transcription / mRNA Capping / mitotic G2 DNA damage checkpoint signaling / Regulation of APC/C activators between G1/S and early anaphase / microtubule organizing center / ubiquitin-like protein ligase binding / RNA Polymerase I Transcription Initiation / regulation of G1/S transition of mitotic cell cycle / regulation of embryonic development / peptidyl-threonine phosphorylation / RNA polymerase II transcribes snRNA genes / protein deubiquitination / positive regulation of G2/M transition of mitotic cell cycle / response to cadmium ion / cyclin-dependent kinase / ATP-dependent activity, acting on DNA / response to mechanical stimulus / cyclin-dependent protein serine/threonine kinase activity / Tat-mediated elongation of the HIV-1 transcript / response to axon injury / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / Formation of HIV-1 elongation complex containing HIV-1 Tat / Regulation of MITF-M-dependent genes involved in cell cycle and proliferation / 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 / positive regulation of cardiac muscle cell proliferation / cyclin-dependent protein kinase holoenzyme complex 類似検索 - 分子機能
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.