Abstract：
:Kinase inhibitors represent the backbone of targeted cancer therapy, yet only a limited number of oncogenic drivers are directly druggable. By interrogating the activity of 1,505 kinase inhibitors, we found that BRD4-NUT-rearranged NUT midline carcinoma (NMC) cells are specifically killed by CDK9 inhibition (CDK9i) and depend on CDK9 and Cyclin-T1 expression. We show that CDK9i leads to robust induction of apoptosis and of markers of DNA damage response in NMC cells. While both CDK9i and bromodomain inhibition over time result in reduced Myc protein expression, only bromodomain inhibition induces cell differentiation and a p21-induced cell-cycle arrest in these cells. Finally, RNA-seq and ChIP-based analyses reveal a BRD4-NUT-specific CDK9i-induced perturbation of transcriptional elongation. Thus, our data provide a mechanistic basis for the genotype-dependent vulnerability of NMC cells to CDK9i that may be of relevance for the development of targeted therapies for NMC patients.
journal_name
Cell Repjournal_title
Cell reportsauthors
Brägelmann J,Dammert MA,Dietlein F,Heuckmann JM,Choidas A,Böhm S,Richters A,Basu D,Tischler V,Lorenz C,Habenberger P,Fang Z,Ortiz-Cuaran S,Leenders F,Eickhoff J,Koch U,Getlik M,Termathe M,Sallouh M,Greff Z,Varga Zdoi
10.1016/j.celrep.2017.08.082subject
Has Abstractpub_date
2017-09-19 00:00:00pages
2833-2845issue
12issn
2211-1247pii
S2211-1247(17)31224-Xjournal_volume
20pub_type
杂志文章相关文献
Cell Reports文献大全abstract：:Here, we examine the mechanism by which plasmacytoid dendritic cells (pDCs) and type I interferons promote humoral autoimmunity. In an amyloid-induced experimental autoimmune model, neutrophil depletion enhanced anti-nuclear antibody development, which correlated with heightened IFN-γ production by natural killer (NK)...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.07.021
更新日期：2015-08-18 00:00:00
abstract：:Despite the comprehensive knowledge on odor coding, our understanding of the relationship between sensory input and behavioral output in Drosophila remains weak. Here, we measure the behavioral responses generated by larval and adult flies in response to 34 fruit odors and find that larval preference for fruit odors d...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.04.085
更新日期：2018-05-22 00:00:00
abstract：:DNA double-strand break repair by homologous recombination entails the resection of DNA ends to reveal ssDNA tails, which are used to invade a homologous DNA template. CtIP and its yeast ortholog Sae2 regulate the nuclease activity of MRE11 in the initial stage of resection. Deletion of CtIP in the mouse or SAE2 in ye...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2017.09.048
更新日期：2017-10-10 00:00:00
abstract：:High-grade serous ovarian carcinoma (HGSOC) originates mainly from the fallopian tube (FT) epithelium and always carries early TP53 mutations. We previously reported that tumors initiate in the FT fimbria epithelium because of apoptotic failure and the expansion of cells with DNA double-strand breaks (DSB) caused by b...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2017.02.049
更新日期：2017-03-14 00:00:00
abstract：:Changes in epigenetic states affect organismal homeostasis, including stress resistance. However, the mechanisms coordinating epigenetic states and systemic stress resistance remain largely unknown. Here, we identify the intestine-to-germline communication of epigenetic states, which intergenerationally enhances stres...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.02.050
更新日期：2020-03-10 00:00:00
abstract：:Adipocytes deficient in fatty acid synthase (iAdFASNKO) emit signals that mimic cold exposure to enhance the appearance of thermogenic beige adipocytes in mouse inguinal white adipose tissues (iWATs). Both cold exposure and iAdFASNKO upregulate the sympathetic nerve fiber (SNF) modulator Neuregulin 4 (Nrg4), activate ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.107998
更新日期：2020-08-04 00:00:00
abstract：:The histone lysine demethylase KDM4C is often overexpressed in cancers primarily through gene amplification. The molecular mechanisms of KDM4C action in tumorigenesis are not well defined. Here, we report that KDM4C transcriptionally activates amino acid biosynthesis and transport, leading to a significant increase in...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.12.053
更新日期：2016-01-26 00:00:00
abstract：:Nuclear factor κB (NF-κB) RelA is the potent transcriptional activator of inflammatory response genes. We stringently defined a list of direct RelA target genes by integrating physical (chromatin immunoprecipitation sequencing [ChIP-seq]) and functional (RNA sequencing [RNA-seq] in knockouts) datasets. We then dissect...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.01.108
更新日期：2020-02-25 00:00:00
abstract：:Either caspase-1 or caspase-11 can cleave gasdermin D to cause pyroptosis, eliminating intracellular replication niches. We previously showed that macrophages detect Burkholderia thailandensis via NLRC4, triggering the release of interleukin (IL)-18 and driving an essential interferon (IFN)-γ response that primes casp...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.107967
更新日期：2020-07-28 00:00:00
abstract：:Generating mammalian cells with desired mitochondrial DNA (mtDNA) sequences is enabling for studies of mitochondria, disease modeling, and potential regenerative therapies. MitoPunch, a high-throughput mitochondrial transfer device, produces cells with specific mtDNA-nuclear DNA (nDNA) combinations by transferring iso...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108562
更新日期：2020-12-29 00:00:00
abstract：:Escape responses to threatening stimuli are vital for survival in all animal species. Larval zebrafish display fast escape responses when exposed to tactile, acoustic, and visual stimuli. However, their behavioral responses to chemosensory stimuli remain unknown. In this study, we found that carbon dioxide (CO2) induc...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.01.019
更新日期：2018-01-30 00:00:00
abstract：:In Drosophila larvae, the class IV dendritic arborization (da) neurons are polymodal nociceptors. Here, we show that ppk26 (CG8546) plays an important role in mechanical nociception in class IV da neurons. Our immunohistochemical and functional results demonstrate that ppk26 is specifically expressed in class IV da ne...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.10.020
更新日期：2014-11-20 00:00:00
abstract：:Accumulation of toxic amyloid oligomers is a key feature in the pathogenesis of amyloid-related diseases. Formation of mature amyloid fibrils is one defense mechanism to neutralize toxic prefibrillar oligomers. This mechanism is notably influenced by apolipoprotein E variants. Cells that produce mature amyloid fibrils...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.08.057
更新日期：2015-10-06 00:00:00
abstract：:The stress-activated protein kinases c-Jun N-terminal kinase (JNK) and p38 are important players in cell-fate decisions in response to environmental stress signals. Crosstalk signaling between JNK and p38 is emerging as an important regulatory mechanism in inflammatory and stress responses. However, it is unknown how ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.08.020
更新日期：2018-09-04 00:00:00
abstract：:Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone involved in nutrient homeostasis. GIP receptor (GIPR) is constitutively internalized and returned to the plasma membrane, atypical behavior for a G-protein-coupled receptor (GPCR). GIP promotes GIPR downregulation from the plasma membrane by inh...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.11.050
更新日期：2016-12-13 00:00:00
abstract：:Hippocampal sharp-wave ripples (SPW-Rs) support consolidation of recently acquired episodic memories and planning future actions by generating ordered neuronal sequences of previous or future experiences. SPW-Rs are characterized by several spectral components: a slow (5-15 Hz) sharp-wave, a high-frequency "ripple" os...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.10.066
更新日期：2018-11-13 00:00:00
abstract：:The multiple functions of lysosomes are critically dependent on their ability to undergo bidirectional movement along microtubules between the center and the periphery of the cell. Centrifugal and centripetal movement of lysosomes is mediated by kinesin and dynein motors, respectively. We recently described a multi-su...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.10.062
更新日期：2016-11-15 00:00:00
abstract：:The flat bones of the skull are densely innervated during development, but little is known regarding their role during repair. We describe a neurotrophic mechanism that directs sensory nerve transit in the mouse calvaria. Patent cranial suture mesenchyme represents an NGF (nerve growth factor)-rich domain, in which se...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.107696
更新日期：2020-05-26 00:00:00
abstract：:Effective approaches to neuropsychiatric disorders require detailed understanding of the cellular composition and circuitry of the complex mammalian brain. Here, we present a paradigm for deconstructing the diversity of neurons defined by a specific neurotransmitter using a microfluidic dynamic array to simultaneously...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.10.008
更新日期：2014-11-06 00:00:00
abstract：:Mitochondrial respiratory chain disorders are characterized by loss of electron transport chain (ETC) activity. Although the causes of many such diseases are known, there is a lack of effective therapies. To identify genes that confer resistance to severe ETC dysfunction when inactivated, we performed a genome-wide ge...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.02.046
更新日期：2014-04-10 00:00:00
abstract：:Mural cells (pericytes and vascular smooth muscle cells) are essential for the regulation of vascular networks and maintenance of vascular integrity, but their origins are diverse in different tissues and not known in the organs that arise from the ectoderm, such as skin. Here, we show that tissue-localized myeloid pr...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2017.02.069
更新日期：2017-03-21 00:00:00
abstract：:Embryonic stem cells (ESCs) exhibit high levels of ribosomal RNA (rRNA) transcription and ribosome biogenesis. Here, we reveal an unexpected role for an essential DEAD-box helicase, DDX18, in antagonizing the polycomb repressive complex 2 (PRC2) to prevent deposition of the repressive H3K27me3 mark onto rDNA in plurip...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.12.021
更新日期：2020-01-07 00:00:00
abstract：:The 26S proteasome is the central ATP-dependent protease in eukaryotes and is essential for organismal health. Proteasome assembly is mediated by several dedicated, evolutionarily conserved chaperone proteins. These chaperones associate transiently with assembly intermediates but are absent from mature proteasomes. Ch...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.12.042
更新日期：2019-01-08 00:00:00
abstract：:Spatiotemporal control of gene expression is crucial for development and subject to evolutionary changes. Although proteins are the final product of most genes, the developmental proteome of an animal has not yet been comprehensively defined, and the correlation between mRNA and protein abundance during development is...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.01.001
更新日期：2014-02-13 00:00:00
abstract：:Measurements of flow velocities at the level of individual arterial vessels and sinusoidal capillaries are crucial for understanding the dynamics of hematopoietic stem and progenitor cell homing in the bone marrow vasculature. We have developed two complementary intravital two-photon imaging approaches to determine bl...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2017.01.042
更新日期：2017-02-14 00:00:00
abstract：:Recent studies have shown that lysines can be posttranslationally modified by various types of acylations. However, except for acetylation, very little is known about their scope and cellular distribution. We mapped thousands of succinylation sites in bacteria (E. coli), yeast (S. cerevisiae), human (HeLa) cells, and ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2013.07.024
更新日期：2013-08-29 00:00:00
abstract：:Chromatin states must be maintained during cell proliferation to uphold cellular identity and genome integrity. Inheritance of histone modifications is central in this process. However, the histone modification landscape is challenged by incorporation of new unmodified histones during each cell cycle, and the principl...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.12.060
更新日期：2020-01-28 00:00:00
abstract：:In metazoans, the nuclear envelope (NE) breakdown (NEBD) occurs during "open" mitosis and meiosis. In the fission yeast Schizosaccharomyces pombe, the mitosis and the first meiotic division (MI) are "closed," during which the NE is maintained. Intriguingly, during the second meiotic division (MII), the NE is also main...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.03.073
更新日期：2018-04-24 00:00:00
abstract：:5-hydroxymethylcytosine (5hmC) is enriched in brain and has been recognized as an important DNA modification. However, the roles of 5hmC and its writers, ten-eleven translocation (Tet) proteins, in stress-induced response have yet to be elucidated. Here, we show that chronic restraint stress (CRS) induced depression-l...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.11.061
更新日期：2018-12-11 00:00:00
abstract：:The vascular endothelial growth factor-A (VEGF-A)-VEGFR2 pathway drives tumor vascularization by activating proangiogenic signaling in endothelial cells (ECs). Here, we show that EC-sphingosine-1-phosphate receptor 1 (S1PR1) amplifies VEGFR2-mediated angiogenic signaling to enhance tumor growth. We show that cancer ce...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.11.036
更新日期：2019-12-10 00:00:00
