Dissecting the Pol II transcription cycle and derailing cancer with CDK inhibitors

How the cell cycle clock ticks

(2019) Mihkel Örd et al.   MOLECULAR BIOLOGY OF THE CELL

MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation

(2019) Apoorva Baluapuri et al.   MOLECULAR CELL

P-TEFb Activation by RBM7 Shapes a Pro-survival Transcriptional Response to Genotoxic Stress

(2019) Andrii Bugai et al.   MOLECULAR CELL

Promoter-proximal pausing of RNA polymerase II: a nexus of gene regulation

(2019) Leighton Core et al.   GENES & DEVELOPMENT

Selective kinase inhibition shows that Bur1 (Cdk9) phosphorylates the Rpb1 linker in vivo

(2019) Yujin Chun et al.   MOLECULAR AND CELLULAR BIOLOGY

TFIIE orchestrates the recruitment of the TFIIH kinase module at promoter before release during transcription

(2019) Emmanuel Compe et al.   Nature Communications

CDK12 loss in cancer cells affects DNA damage response genes through premature cleavage and polyadenylation

(2019) Malgorzata Krajewska et al.   Nature Communications

Therapeutic Targeting of CDK12/CDK13 in Triple-Negative Breast Cancer

(2019) Victor Quereda et al.   CANCER CELL

Control of RNA Pol II Speed by PNUTS-PP1 and Spt5 Dephosphorylation Facilitates Termination by a “Sitting Duck Torpedo” Mechanism

(2019) Michael A. Cortazar et al.   MOLECULAR CELL

Cdk9 regulates a promoter-proximal checkpoint to modulate RNA polymerase II elongation rate in fission yeast

(2018) Gregory T. Booth et al.   Nature Communications

The HIV-1 Tat protein recruits a ubiquitin ligase to reorganize the 7SK snRNP for transcriptional activation

(2018) Tyler B Faust et al.   eLife

Small Molecules Co-targeting CKIα and the Transcriptional Kinases CDK7/9 Control AML in Preclinical Models

(2018) Waleed Minzel et al.   CELL

A Cdk9–PP1 switch regulates the elongation–termination transition of RNA polymerase II

(2018) Pabitra K. Parua et al.   NATURE

Structure of paused transcription complex Pol II–DSIF–NELF

(2018) Seychelle M. Vos et al.   NATURE

Structure of activated transcription complex Pol II–DSIF–PAF–SPT6

(2018) Seychelle M. Vos et al.   NATURE

CTD-dependent and -independent mechanisms govern co-transcriptional capping of Pol II transcripts

(2018) Melvin Noe Gonzalez et al.   Nature Communications

CDK12 regulates DNA repair genes by suppressing intronic polyadenylation

(2018) Sara J. Dubbury et al.   NATURE

Noncanonical CTD kinases regulate RNA polymerase II in a gene-class-specific manner

(2018) Corey M. Nemec et al.   Nature Chemical Biology

Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation

(2017) Calla M Olson et al.   Nature Chemical Biology

Synthetic lethality and cancer

(2017) Nigel J. O'Neil et al.   NATURE REVIEWS GENETICS

CDK12 regulates alternative last exon mRNA splicing and promotes breast cancer cell invasion

(2017) Jerry F. Tien et al.   NUCLEIC ACIDS RESEARCH

CDK8 Kinase Activity Promotes Glycolysis

(2017) Matthew D. Galbraith et al.   Cell Reports

Human TFIIH Kinase CDK7 Regulates Transcription-Associated Chromatin Modifications

(2017) Christopher C. Ebmeier et al.   Cell Reports

Activation of the p53 Transcriptional Program Sensitizes Cancer Cells to Cdk7 Inhibitors

(2017) Sampada Kalan et al.   Cell Reports

CDK9-dependent RNA polymerase II pausing controls transcription initiation

(2017) Saskia Gressel et al.   eLife

P-TEFb regulation of transcription termination factor Xrn2 revealed by a chemical genetic screen for Cdk9 substrates

(2016) Miriam Sansó et al.   GENES & DEVELOPMENT

KAP1 Recruitment of the 7SK snRNP Complex to Promoters Enables Transcription Elongation by RNA Polymerase II

(2016) Ryan P. McNamara et al.   MOLECULAR CELL

Engineered Covalent Inactivation of TFIIH-Kinase Reveals an Elongation Checkpoint and Results in Widespread mRNA Stabilization

(2016) Juan B. Rodríguez-Molina et al.   MOLECULAR CELL

Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors

(2016) Tinghu Zhang et al.   Nature Chemical Biology

Induced protein degradation: an emerging drug discovery paradigm

(2016) Ashton C. Lai et al.   NATURE REVIEWS DRUG DISCOVERY

Structural and Functional Analysis of the Cdk13/Cyclin K Complex

(2016) Ann Katrin Greifenberg et al.   Cell Reports

CDK12 Inhibition Reverses De Novo and Acquired PARP Inhibitor Resistance in BRCA Wild-Type and Mutated Models of Triple-Negative Breast Cancer

(2016) Shawn F. Johnson et al.   Cell Reports

Engineering an analog-sensitive CDK12 cell line using CRISPR/Cas

(2015) Bartlomiej Bartkowiak et al.   Biochimica et Biophysica Acta-Gene Regulatory Mechanisms

CDK7-Dependent Transcriptional Addiction in Triple-Negative Breast Cancer

(2015) Yubao Wang et al.   CELL

Characterization of Human Cyclin-Dependent Kinase 12 (CDK12) and CDK13 Complexes in C-Terminal Domain Phosphorylation, Gene Transcription, and RNA Processing

(2015) Kaiwei Liang et al.   MOLECULAR AND CELLULAR BIOLOGY

Fission Yeast Cdk7 Controls Gene Expression through both Its CAK and C-Terminal Domain Kinase Activities

(2015) Maxime Devos et al.   MOLECULAR AND CELLULAR BIOLOGY

THZ1 Reveals Roles for Cdk7 in Co-transcriptional Capping and Pausing

(2015) Kyle A. Nilson et al.   MOLECULAR CELL

Mediator kinase inhibition further activates super-enhancer-associated genes in AML

(2015) Henry E. Pelish et al.   NATURE

CDK9 inhibitors define elongation checkpoints at both ends of RNA polymerase II–transcribed genes

(2015) Clélia Laitem et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

CDK9 inhibitors define elongation checkpoints at both ends of RNA polymerase II–transcribed genes

(2015) Clélia Laitem et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Gene looping facilitates TFIIH kinase-mediated termination of transcription

(2015) Scott Medler et al.   Scientific Reports

Compensatory induction of MYC expression by sustained CDK9 inhibition via a BRD4-dependent mechanism

(2015) Huasong Lu et al.   eLife

Targeting Transcriptional Addictions in Small Cell Lung Cancer with a Covalent CDK7 Inhibitor

(2014) Camilla L. Christensen et al.   CANCER CELL

CDK7 Inhibition Suppresses Super-Enhancer-Linked Oncogenic Transcription in MYCN-Driven Cancer

(2014) Edmond Chipumuro et al.   CELL

3' end formation of pre-mRNA and phosphorylation of Ser2 on the RNA polymerase II CTD are reciprocally coupled in human cells

(2014) L. Davidson et al.   GENES & DEVELOPMENT

Cyclin-Dependent Kinase 12 Increases 3′ End Processing of Growth Factor-Induced c-FOS Transcripts

(2014) Tristan T. Eifler et al.   MOLECULAR AND CELLULAR BIOLOGY

TFIIH Phosphorylation of the Pol II CTD Stimulates Mediator Dissociation from the Preinitiation Complex and Promoter Escape

(2014) Koon Ho Wong et al.   MOLECULAR CELL

Targeting transcription regulation in cancer with a covalent CDK7 inhibitor

(2014) Nicholas Kwiatkowski et al.   NATURE

RNA helicase DDX21 coordinates transcription and ribosomal RNA processing

(2014) Eliezer Calo et al.   NATURE

The structure and substrate specificity of human Cdk12/Cyclin K

(2014) Christian A. Bösken et al.   Nature Communications

Cyclin-dependent kinases

(2014) Marcos Malumbres   GENOME BIOLOGY

Brd4 and JMJD6-Associated Anti-Pause Enhancers in Regulation of Transcriptional Pause Release

(2013) Wen Liu et al.   CELL

HIF1A Employs CDK8-Mediator to Stimulate RNAPII Elongation in Response to Hypoxia

(2013) Matthew D. Galbraith et al.   CELL

SR Proteins Collaborate with 7SK and Promoter-Associated Nascent RNA to Release Paused Polymerase

(2013) Xiong Ji et al.   CELL

CDK8 Kinase Phosphorylates Transcription Factor STAT1 to Selectively Regulate the Interferon Response

(2013) Joanna Bancerek et al.   IMMUNITY

Phospho Switch Triggers Brd4 Chromatin Binding and Activator Recruitment for Gene-Specific Targeting

(2013) Shwu-Yuan Wu et al.   MOLECULAR CELL

A conserved Mediator–CDK8 kinase module association regulates Mediator–RNA polymerase II interaction

(2013) Kuang-Lei Tsai et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

RNA Polymerase II Elongation Control

(2012) Qiang Zhou et al.   Annual Review of Biochemistry

The RNA Pol II Elongation Factor Ell3 Marks Enhancers in ES Cells and Primes Future Gene Activation

(2012) Chengqi Lin et al.   CELL

The RNA polymerase II CTD coordinates transcription and RNA processing

(2012) J.-P. Hsin et al.   GENES & DEVELOPMENT

Cyclin K-containing Kinase Complexes Maintain Self-renewal in Murine Embryonic Stem Cells

(2012) Qian Dai et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Separate Domains of Fission Yeast Cdk9 (P-TEFb) Are Required for Capping Enzyme Recruitment and Primed (Ser7-Phosphorylated) Rpb1 Carboxyl-Terminal Domain Substrate Recognition

(2012) C. V. St. Amour et al.   MOLECULAR AND CELLULAR BIOLOGY

Cyclin-dependent kinase control of the initiation-to-elongation switch of RNA polymerase II

(2012) Stéphane Larochelle et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Serine-7 but not serine-5 phosphorylation primes RNA polymerase II CTD for P-TEFb recognition

(2012) Nadine Czudnochowski et al.   Nature Communications

A Positive Feedback Loop Links Opposing Functions of P-TEFb/Cdk9 and Histone H2B Ubiquitylation to Regulate Transcript Elongation in Fission Yeast

(2012) Miriam Sansó et al.   PLoS Genetics

The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes

(2011) D. Blazek et al.   GENES & DEVELOPMENT

The Initiation Factor TFE and the Elongation Factor Spt4/5 Compete for the RNAP Clamp during Transcription Initiation and Elongation

(2011) Dina Grohmann et al.   MOLECULAR CELL

Insights into the function of the human P-TEFb component CDK9 in the regulation of chromatin modifications and co-transcriptional mRNA processing

(2010) Judith Pirngruber et al.   CELL CYCLE

CDK12 is a transcription elongation-associated CTD kinase, the metazoan ortholog of yeast Ctk1

(2010) B. Bartkowiak et al.   GENES & DEVELOPMENT

CDK8 is a positive regulator of transcriptional elongation within the serum response network

(2010) Aaron J Donner et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Nuclear CDKs Drive Smad Transcriptional Activation and Turnover in BMP and TGF-β Pathways

(2009) Claudio Alarcón et al.   CELL

Acetylation of cyclin T1 regulates the equilibrium between active and inactive P-TEFb in cells

(2009) Sungyoo Cho et al.   EMBO JOURNAL

TFIIH-Associated Cdk7 Kinase Functions in Phosphorylation of C-Terminal Domain Ser7 Residues, Promoter-Proximal Pausing, and Termination by RNA Polymerase II

(2009) K. Glover-Cutter et al.   MOLECULAR AND CELLULAR BIOLOGY

TFIIH Kinase Places Bivalent Marks on the Carboxy-Terminal Domain of RNA Polymerase II

(2009) Md. Sohail Akhtar et al.   MOLECULAR CELL

Progression through the RNA Polymerase II CTD Cycle

(2009) Stephen Buratowski   MOLECULAR CELL

TFIIH and P-TEFb Coordinate Transcription with Capping Enzyme Recruitment at Specific Genes in Fission Yeast

(2009) Laia Viladevall et al.   MOLECULAR CELL

E2F1 represses β-catenin transcription and is antagonized by both pRB and CDK8

(2008) Erick J. Morris et al.   NATURE