Abstract：
:Recurrent copy-number alterations, mutations, and transcript fusions of the genes encoding CDKs/cyclins are characterized in >10,000 tumors. Genomic alterations of CDKs/cyclins are dominantly driven by copy number aberrations. In contrast to cell-cycle-related CDKs/cyclins, which are globally amplified, transcriptional CDKs/cyclins recurrently lose copy numbers across cancers. Although mutations and transcript fusions are relatively rare events, CDK12 exhibits recurrent mutations in multiple cancers. Among the transcriptional CDKs, CDK7 and CDK12 show the most significant copy number loss and mutation, respectively. Their genomic alterations are correlated with increased sensitivities to DNA-damaging drugs. Inhibition of CDK7 preferentially represses the expression of genes in the DNA-damage-repair pathways and impairs the activity of homologous recombination. Low-dose CDK7 inhibitor treatment sensitizes cancer cells to PARP inhibitor-induced DNA damage and cell death. Our analysis provides genomic information for identification and prioritization of drug targets for CDKs and reveals rationales for treatment strategies.
journal_name
Cell Repjournal_title
Cell reportsauthors
Shan W,Yuan J,Hu Z,Jiang J,Wang Y,Loo N,Fan L,Tang Z,Zhang T,Xu M,Pan Y,Lu J,Long M,Tanyi JL,Montone KT,Fan Y,Hu X,Zhang Y,Zhang Ldoi
10.1016/j.celrep.2020.107884subject
Has Abstractpub_date
2020-07-14 00:00:00pages
107884issue
2issn
2211-1247pii
S2211-1247(20)30865-2journal_volume
32pub_type
杂志文章相关文献
Cell Reports文献大全abstract：:Naproxen is a non-steroidal anti-inflammatory drug that has previously been shown to exert antiviral activity against influenza A virus by inhibiting nucleoprotein (NP) binding to RNA. Here, we show that naproxen is a potential broad, multi-mechanistic anti-influenza virus therapeutic, as it inhibits influenza B virus...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.04.053
更新日期：2019-05-07 00:00:00
abstract：:Circularization was recently recognized to broadly expand transcriptome complexity. Here, we exploit massive Drosophila total RNA-sequencing data, >5 billion paired-end reads from >100 libraries covering diverse developmental stages, tissues, and cultured cells, to rigorously annotate >2,500 fruit fly circular RNAs. T...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.10.062
更新日期：2014-12-11 00:00:00
abstract：:Despite recent progress in engineering native trimeric HIV-1 envelope glycoprotein (Env) mimics as vaccine candidates, Env trimers often induce vaccine-matched neutralizing antibody (NAb) responses. Understanding the specificities of autologous NAb responses and the underlying molecular mechanisms restricting the neut...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.03.039
更新日期：2019-04-09 00:00:00
abstract：:A new influenza-like virus genome (H17N10) was recently discovered in bats and offers a new perspective about the origin and evolution of influenza viruses. The viral envelope glycoprotein hemagglutinin (HA) is responsible for influenza virus receptor binding, fusion, and entry into the cell; therefore, the structure ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2013.01.025
更新日期：2013-03-28 00:00:00
abstract：:Telomerase biogenesis is a complex process where several steps remain poorly understood. Single-strand-selective uracil-DNA glycosylase (SMUG1) associates with the DKC1-containing H/ACA ribonucleoprotein complex, which is essential for telomerase biogenesis. Herein, we show that SMUG1 interacts with the telomeric RNA ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.07.040
更新日期：2019-08-13 00:00:00
abstract：:Many autoimmune and infectious diseases are characterized by the formation of granulomas which are inflammatory lesions that consist of spatially organized immune cells. These sites protect the host and control pathogens like Mycobacterium tuberculosis (Mtb), but are highly inflammatory and cause pathology. Using baci...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.04.072
更新日期：2019-05-14 00:00:00
abstract：:Neuregulin-1 (NRG1) gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions in vivo...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.07.026
更新日期：2014-08-21 00:00:00
abstract：:Thymic epithelial cells (TECs) are critically required for T cell development, but the cellular mechanisms that maintain adult TECs are poorly understood. Here, we show that a previously unidentified subpopulation, EpCam(+)UEA1(-)Ly-51(+)PLET1(+)MHC class II(hi), which comprises <0.5% of adult TECs, contains bipotent ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.02.080
更新日期：2016-03-29 00:00:00
abstract：:BRCA1 is a tumor suppressor found to be mutated in hereditary breast and ovarian cancer and plays key roles in the maintenance of genomic stability by homologous recombination repair. It is recruited to damaged chromatin as a component of the BRCA1-A deubiquitinase, which cleaves K63-linked ubiquitin chains attached t...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.11.063
更新日期：2016-12-20 00:00:00
abstract：:Activity-dependent modifications strongly influence neural development. However, molecular programs underlying their context and circuit-specific effects are not well understood. To study global transcriptional changes associated with chronic elevation of synaptic activity, we performed cell-type-specific transcriptom...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.10.016
更新日期：2018-10-30 00:00:00
abstract：:Memory B cells (MBCs) epitomize the adaptation of the immune system to the environment. We identify two MBC subsets in peripheral blood, CD27dull and CD27bright MBCs, whose frequency changes with age. Heavy chain variable region (VH) usage, somatic mutation frequency replacement-to-silent ratio, and CDR3 property chan...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.02.022
更新日期：2020-03-03 00:00:00
abstract：:While interphase mitochondria associate with microtubules, mitotic mitochondria dissociate from spindle microtubules and localize in the cell periphery. Here, we show that this redistribution is not mediated by mitochondrial active transport or tethering to the cytoskeleton. Instead, kinesin and dynein, which link mit...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.07.055
更新日期：2016-08-23 00:00:00
abstract：:Horizontal transmission of the microbiota between different individuals is widely used to normalize the microbiota in laboratory mice. However, little is known about the dynamics of microbial communities and the level of microbiota transmission after cohousing. We extensively analyzed the fecal microbiota in Jackson a...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.05.042
更新日期：2019-06-11 00:00:00
abstract：:T follicular helper (Tfh) cells are crucial for the establishment of germinal centers (GCs) and potent antibody responses. Nevertheless, the T cell-intrinsic factors that are required for the maintenance of already-established Tfh cells and GCs remain largely unknown. Here, we use temporally guided gene ablation in CD...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108232
更新日期：2020-10-06 00:00:00
abstract：:Hypertrophic cardiomyopathy (HCM) is a heritable cardiovascular disorder that affects 1 in 500 people. A significant percentage of HCM is attributed to mutations in β-cardiac myosin, the motor protein that powers ventricular contraction. This study reports how two early-onset HCM mutations, D239N and H251N, affect the...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.11.040
更新日期：2016-12-13 00:00:00
abstract：:Hypoxia-inducible factors (HIFs) are critical regulators of the cellular response to hypoxia. Despite their established roles in normal physiology and numerous pathologies, the molecular mechanisms by which they control gene expression remain poorly understood. We report here a conserved role for the TIP60 complex as ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.05.082
更新日期：2016-06-28 00:00:00
abstract：:STAT5, a member of the family of signal transducers and activators of transcription, senses cytokines and controls the biology of cell lineages, including mammary, liver, and T cells. Here, we show that STAT5 activates lineage-specific and widely expressed genes through different mechanisms. STAT5 preferentially binds...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.11.079
更新日期：2016-12-20 00:00:00
abstract：:One puzzling observation in patients affected with Hutchinson-Gilford progeria syndrome (HGPS), who overall exhibit systemic and dramatic premature aging, is the absence of any conspicuous cognitive impairment. Recent studies based on induced pluripotent stem cells derived from HGPS patient cells have revealed a lack ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2012.05.015
更新日期：2012-07-26 00:00:00
abstract：:The corpus callosum is the major axon tract that connects and integrates neural activity between the two cerebral hemispheres. Although ∼1:4,000 children are born with developmental absence of the corpus callosum, the primary etiology of this condition remains unknown. Here, we demonstrate that midline crossing of cal...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.09.033
更新日期：2016-10-11 00:00:00
abstract：:Insulin stimulates glucose uptake through the membrane translocation of GLUT4 and GLUT1. Peroxisome proliferator-activated receptor γ (PPARγ) enhances insulin sensitivity. Here, we demonstrate that insulin stimulates GLUT4 and GLUT1 translocation, and glucose uptake, by activating the signaling pathway involving nicot...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2012.10.018
更新日期：2012-12-27 00:00:00
abstract：:Current treatment regimens for pancreatic ductal adenocarcinoma (PDAC) yield poor 5-year survival, emphasizing the critical need to identify druggable targets essential for PDAC maintenance. We developed an unbiased and in vivo target discovery approach to identify molecular vulnerabilities in low-passage and patient-...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.05.063
更新日期：2016-06-28 00:00:00
abstract：:Sirtuin 2 is a nicotinamide-adenine-dinucleotide-dependent deacetylase that regulates cell processes such as carcinogenesis, cell cycle, DNA damage, and infection. Subcellular localization of SIRT2 is crucial for its function but is poorly understood. Infection with the bacterial pathogen Listeria monocytogenes, which...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.03.116
更新日期：2018-04-24 00:00:00
abstract：:Stable unannotated transcripts (SUTs), some of which overlap protein-coding genes in antisense direction, are a class of non-coding RNAs. While case studies have reported important regulatory roles for several of such RNAs, their general impact on protein abundance regulation of the overlapping gene is not known. To t...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.05.043
更新日期：2016-06-21 00:00:00
abstract：:The quality of mitochondria in skeletal muscle is essential for maintaining metabolic homeostasis during adaptive stress responses. However, the precise control mechanism of muscle mitochondrial quality and its physiological impacts remain unclear. Here, we demonstrate that FUNDC1, a mediator of mitophagy, plays a cri...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.03.127
更新日期：2018-05-01 00:00:00
abstract：:The JAK/STAT1 pathway is generally activated by cytokines, providing essential antiviral defense. Here, we identify that STAT1 activation is independent of cytokines and JAKs at the early infection stage of some viruses, including influenza A virus (IAV). Instead, STAT1 is activated mainly through spleen tyrosine kina...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108627
更新日期：2021-01-19 00:00:00
abstract：:Emerging studies have begun to demonstrate that reprogrammed stromal cells play pivotal roles in tumor growth, metastasis, and resistance to therapy. However, the contribution of stromal cells to non-small-cell lung cancer (NSCLC) has remained underexplored. We used an orthotopic model of Kras-driven NSCLC to systemat...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.01.040
更新日期：2015-02-24 00:00:00
abstract：:Training-dependent increases in c-fos have been used to identify engram cells encoding long-term memories (LTMs). However, the interaction between transcription factors required for LTM, including CREB and c-Fos, and activating kinases such as phosphorylated ERK (pERK) in the establishment of memory engrams has been u...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.11.022
更新日期：2018-12-04 00:00:00
abstract：:Antimetabolites that affect nucleotide metabolism are frontline chemotherapy agents in several cancers and often successfully target one carbon metabolism. However, the precise mechanisms and resulting determinants of their therapeutic value are unknown. We show that 5-fluorouracil (5-FU), a commonly used antimetaboli...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.05.035
更新日期：2016-06-14 00:00:00
abstract：:Common fragile sites (CFSs) are genomic regions that display gaps and breaks in human metaphase chromosomes under replication stress and are often deleted in cancer cells. We studied an ∼300-bp subregion (Flex1) of human CFS FRA16D in yeast and found that it recapitulates characteristics of CFS fragility in human cell...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.03.103
更新日期：2019-04-23 00:00:00
abstract：:Ubiquitin and ubiquitin-like chains are finely balanced by conjugating and de-conjugating enzymes. Alterations in this balance trigger the response to stress conditions and are often observed in pathologies. How such changes are detected is not well understood. We identify the HSP70 chaperone as a sensor of changes in...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.08.070
更新日期：2019-10-01 00:00:00
