The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted therapeutically in cancer

Phosphoproteome and drug response effects mediated by the three Protein Phosphatase 2A inhibitor proteins CIP2A, SET and PME-1

(2020) Otto Kauko et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

P-TEFb as A Promising Therapeutic Target

(2020) Koh Fujinaga   MOLECULES

DAF-16/FOXO requires Protein Phosphatase 4 to initiate transcription of stress resistance and longevity promoting genes

(2020) Ilke Sen et al.   Nature Communications

Transcription-Associated Cyclin-Dependent Kinases as Targets and Biomarkers for Cancer Therapy

(2020) Jonathan Chou et al.   Cancer Discovery

Allosteric Activators of Protein Phosphatase 2A Display Broad Antitumor Activity Mediated by Dephosphorylation of MYBL2

(2020) Ken Morita et al.   CELL

Piecing Together a Broken Tumor Suppressor Phosphatase for Cancer Therapy

(2020) Jukka Westermarck et al.   CELL

Selective PP2A Enhancement through Biased Heterotrimer Stabilization

(2020) Daniel Leonard et al.   CELL

Targeted chemotherapy overcomes drug resistance in melanoma

(2020) Jingyin Yue et al.   GENES & DEVELOPMENT

Therapeutic Targeting of the General RNA Polymerase II Transcription Machinery

(2020) Ryan D. Martin et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

The Human Integrator Complex Facilitates Transcriptional Elongation by Endonucleolytic Cleavage of Nascent Transcripts

(2020) Felipe Beckedorff et al.   Cell Reports

Recent Developments in the Biology and Medicinal Chemistry of CDK9 Inhibitors: An Update

(2020) Tizhi Wu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Integrator Recruits Protein Phosphatase 2A to Prevent Pause Release and Facilitate Transcription Termination

(2020) Kai-Lieh Huang et al.   MOLECULAR CELL

Distinct Cdk9-phosphatase switches act at the beginning and end of elongation by RNA polymerase II

(2020) Pabitra K. Parua et al.   Nature Communications

Identification of Integrator-PP2A complex (INTAC), an RNA polymerase II phosphatase

(2020) Hai Zheng et al.   SCIENCE

Integrator is a key component of human telomerase RNA biogenesis

(2019) M. P. Rubtsova et al.   Scientific Reports

SCAF4 and SCAF8, mRNA Anti-Terminator Proteins

(2019) Lea H. Gregersen et al.   CELL

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

(2019) Leighton Core et al.   GENES & DEVELOPMENT

Next-generation characterization of the Cancer Cell Line Encyclopedia

(2019) Mahmoud Ghandi et al.   NATURE

Cyclin-dependent kinase-9 is a therapeutic target in MYC-expressing diffuse large B-cell lymphoma

(2019) Taylor Hashiguchi et al.   MOLECULAR CANCER THERAPEUTICS

Protein phosphatase 2A as a therapeutic target in inflammation and neurodegeneration

(2019) Andrew R. Clark et al.   PHARMACOLOGY & THERAPEUTICS

Metascape provides a biologist-oriented resource for the analysis of systems-level datasets

(2019) Yingyao Zhou et al.   Nature Communications

The Integrator complex cleaves nascent mRNAs to attenuate transcription

(2019) Deirdre C. Tatomer et al.   GENES & DEVELOPMENT

50+ years of eukaryotic transcription: an expanding universe of factors and mechanisms

(2019) Robert G. Roeder   NATURE STRUCTURAL & MOLECULAR BIOLOGY

AZD4573 is a highly selective CDK9 inhibitor that suppresses Mcl-1 and induces apoptosis in hematological cancer cells.

(2019) Justin Cidado et al.   CLINICAL CANCER RESEARCH

A unified allosteric/torpedo mechanism for transcriptional termination on human protein-coding genes

(2019) Joshua D. Eaton et al.   GENES & DEVELOPMENT

The Integrator Complex Attenuates Promoter-Proximal Transcription at Protein-Coding Genes

(2019) Nathan D. Elrod et al.   MOLECULAR 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

Targeted Enhancer Activation by a Subunit of the Integrator Complex

(2018) Elisa Barbieri et al.   MOLECULAR CELL

Born to run: control of transcription elongation by RNA polymerase II

(2018) Fei Xavier Chen et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells

(2018) Otto Kauko et al.   Science Translational Medicine

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

Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth

(2017) Jaya Sangodkar et al.   JOURNAL OF CLINICAL INVESTIGATION

Genome-scale CRISPR-Cas9 knockout and transcriptional activation screening

(2017) Julia Joung et al.   Nature Protocols

Architecture of the RNA polymerase II-Paf1C-TFIIS transcription elongation complex

(2017) Youwei Xu et al.   Nature Communications

CDK9-dependent RNA polymerase II pausing controls transcription initiation

(2017) Saskia Gressel et al.   eLife

Robust hyperparameter estimation protects against hypervariable genes and improves power to detect differential expression

(2016) Belinda Phipson et al.   Annals of Applied Statistics

Integrator complex and transcription regulation: Recent findings and pathophysiology

(2016) Monica Rienzo et al.   Biochimica et Biophysica Acta-Gene Regulatory Mechanisms

Dephosphorylating eukaryotic RNA polymerase II

(2016) Joshua E. Mayfield et al.   BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS

Recurrent PPP2R1A Mutations in Uterine Cancer Act through a Dominant-Negative Mechanism to Promote Malignant Cell Growth

(2016) Dorien Haesen et al.   CANCER RESEARCH

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

(2016) Miriam Sansó et al.   GENES & DEVELOPMENT

The RNA Polymerase II CTD: The Increasing Complexity of a Low-Complexity Protein Domain

(2016) Célia Jeronimo et al.   JOURNAL OF MOLECULAR BIOLOGY

Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9

(2016) John G Doench et al.   NATURE BIOTECHNOLOGY

A Modular Assembly Platform for Rapid Generation of DNA Constructs

(2016) Elliot H. Akama-Garren et al.   Scientific Reports

An Alternative Approach to ChIP-Seq Normalization Enables Detection of Genome-Wide Changes in Histone H3 Lysine 27 Trimethylation upon EZH2 Inhibition

(2016) Brian Egan et al.   PLoS One

Reengineered tricyclic anti-cancer agents

(2015) David B. Kastrinsky et al.   BIOORGANIC & MEDICINAL CHEMISTRY

The CDK9 Inhibitor Dinaciclib Exerts Potent Apoptotic and Antitumor Effects in Preclinical Models of MLL-Rearranged Acute Myeloid Leukemia

(2015) A. Baker et al.   CANCER RESEARCH

PAF1, a Molecular Regulator of Promoter-Proximal Pausing by RNA Polymerase II

(2015) Fei Xavier Chen et al.   CELL

Integrator mediates the biogenesis of enhancer RNAs

(2015) Fan Lai et al.   NATURE

HISAT: a fast spliced aligner with low memory requirements

(2015) Daehwan Kim et al.   NATURE METHODS

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

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

RNA polymerase II-associated factor 1 regulates the release and phosphorylation of paused RNA polymerase II

(2015) M. Yu et al.   SCIENCE

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

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

An Inducible Lentiviral Guide RNA Platform Enables the Identification of Tumor-Essential Genes and Tumor-Promoting Mutations In Vivo

(2015) Brandon J. Aubrey et al.   Cell Reports

Bioinformatics analysis of gene expression profiles in childhood B-precursor acute lymphoblastic leukemia

(2015) Jun Li et al.   Hematology

CDK9 inhibition by dinaciclib potently suppresses Mcl-1 to induce durable apoptotic responses in aggressive MYC-driven B-cell lymphoma in vivo

(2015) G P Gregory et al.   LEUKEMIA

Differentiation therapy for the treatment of t(8;21) acute myeloid leukemia using histone deacetylase inhibitors

(2014) M. Bots et al.   BLOOD

Integrator Regulates Transcriptional Initiation and Pause Release following Activation

(2014) Alessandro Gardini et al.   MOLECULAR CELL

Targeting transcription regulation in cancer with a covalent CDK7 inhibitor

(2014) Nicholas Kwiatkowski et al.   NATURE

A PP1–PP2A phosphatase relay controls mitotic progression

(2014) Agnes Grallert et al.   NATURE

Improved vectors and genome-wide libraries for CRISPR screening

(2014) Neville E Sanjana et al.   NATURE METHODS

deepTools: a flexible platform for exploring deep-sequencing data

(2014) Fidel Ramírez et al.   NUCLEIC ACIDS RESEARCH

Quantitative ChIP-Seq Normalization Reveals Global Modulation of the Epigenome

(2014) David A. Orlando et al.   Cell Reports

Cyclin-dependent kinases

(2014) Marcos Malumbres   GENOME BIOLOGY

featureCounts: an efficient general purpose program for assigning sequence reads to genomic features

(2013) Y. Liao et al.   BIOINFORMATICS

Protein phosphatase 2A: a target for anticancer therapy

(2013) Danilo Perrotti et al.   LANCET ONCOLOGY

The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote

(2013) Yang Liao et al.   NUCLEIC ACIDS RESEARCH

Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal

(2013) J. Gao et al.   Science Signaling

Mutagenesis and homologous recombination in Drosophila cell lines using CRISPR/Cas9

(2013) A. R. Bassett et al.   Biology Open

STAR: ultrafast universal RNA-seq aligner

(2012) Alexander Dobin et al.   BIOINFORMATICS

Fast gapped-read alignment with Bowtie 2

(2012) Ben Langmead et al.   NATURE METHODS

Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans

(2012) Karen Adelman et al.   NATURE REVIEWS GENETICS

The super elongation complex (SEC) family in transcriptional control

(2012) Zhuojuan Luo et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Somatic Mutations of PPP2R1A in Ovarian and Uterine Carcinomas

(2011) Ie-Ming Shih et al.   AMERICAN JOURNAL OF PATHOLOGY

RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome

(2011) Bo Li et al.   BMC BIOINFORMATICS

BEDTools: a flexible suite of utilities for comparing genomic features

(2010) Aaron R. Quinlan et al.   BIOINFORMATICS

AFF4, a Component of the ELL/P-TEFb Elongation Complex and a Shared Subunit of MLL Chimeras, Can Link Transcription Elongation to Leukemia

(2010) Chengqi Lin et al.   MOLECULAR CELL

seqMINER: an integrated ChIP-seq data interpretation platform

(2010) Tao Ye et al.   NUCLEIC ACIDS RESEARCH

The Sequence Alignment/Map format and SAMtools

(2009) H. Li et al.   BIOINFORMATICS

INTS6/DICE1 inhibits growth of human androgen-independent prostate cancer cells by altering the cell cycle profile and Wnt signaling

(2009) Stephanie Filleur et al.   Cancer Cell International

Control of Inducible Gene Expression by Signal-Dependent Transcriptional Elongation

(2009) Diana C. Hargreaves et al.   CELL

INTS3 controls the hSSB1-mediated DNA damage response

(2009) Jeffrey R. Skaar et al.   JOURNAL OF CELL BIOLOGY

BioVenn – a web application for the comparison and visualization of biological lists using area-proportional Venn diagrams

(2008) Tim Hulsen et al.   BMC GENOMICS

Model-based Analysis of ChIP-Seq (MACS)

(2008) Yong Zhang et al.   GENOME BIOLOGY