当前位置： SCI文献检索 > MOLECULAR CELL期刊下所有文献 > miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors.

miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors.

Abstract：

:Expression of BRCA1 is commonly decreased in sporadic breast tumors, and this correlates with poor prognosis of breast cancer patients. Here we show that BRCA1 transcripts are selectively enriched in the Argonaute/miR-182 complex and miR-182 downregulates BRCA1 expression. Antagonizing miR-182 enhances BRCA1 protein levels and protects them from IR-induced cell death, while overexpressing miR-182 reduces BRCA1 protein, impairs homologous recombination-mediated repair, and render cells hypersensitive to IR. The impaired DNA repair phenotype induced by miR-182 overexpression can be fully rescued by overexpressing miR-182-insensitive BRCA1. Consistent with a BRCA1-deficiency phenotype, miR-182-overexpressing breast tumor cells are hypersensitive to inhibitors of poly (ADP-ribose) polymerase 1 (PARP1). Conversely, antagonizing miR-182 enhances BRCA1 levels and induces resistance to PARP1 inhibitor. Finally, a clinical-grade PARP1 inhibitor impacts outgrowth of miR-182-expressing tumors in animal models. Together these results suggest that miR-182-mediated downregulation of BRCA1 impedes DNA repair and may impact breast cancer therapy.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Moskwa P,Buffa FM,Pan Y,Panchakshari R,Gottipati P,Muschel RJ,Beech J,Kulshrestha R,Abdelmohsen K,Weinstock DM,Gorospe M,Harris AL,Helleday T,Chowdhury D

doi

10.1016/j.molcel.2010.12.005

subject

Has Abstract

pub_date

2011-01-21 00:00:00

pages

210-20

issue

2

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(10)00961-5

journal_volume

41

pub_type

杂志文章

相关文献

MOLECULAR CELL文献大全
  • Noncooperative interactions between transcription factors and clustered DNA binding sites enable graded transcriptional responses to environmental inputs.

    abstract：:A paradigm in transcriptional regulation is that graded increases in transcription factor (TF) concentration are translated into on/off transcriptional responses by cooperative TF binding to adjacent sites. Digital transcriptional responses underlie the definition of anatomical boundaries during development. Here we s...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2010.01.016

    authors： Giorgetti L,Siggers T,Tiana G,Caprara G,Notarbartolo S,Corona T,Pasparakis M,Milani P,Bulyk ML,Natoli G

    更新日期：2010-02-12 00:00:00

  • Crystal structure of colicin E3: implications for cell entry and ribosome inactivation.

    abstract：:Colicins kill E. coli by a process that involves binding to a surface receptor, entering the cell, and, finally, intoxicating it. The lethal action of colicin E3 is a specific cleavage in the ribosomal decoding A site. The crystal structure of colicin E3, reported here in a binary complex with its immunity protein (IP...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(01)00396-3

    authors： Soelaiman S,Jakes K,Wu N,Li C,Shoham M

    更新日期：2001-11-01 00:00:00

  • Modulation of RNA polymerase assembly dynamics in transcriptional regulation.

    abstract：:The interaction of transcription factors with target genes is highly dynamic. Whether the dynamic nature of these interactions is merely an intrinsic property of transcription factors or serves a regulatory role is unknown. Here we have used single-cell fluorescence imaging combined with computational modeling and chr...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2008.04.021

    authors： Gorski SA,Snyder SK,John S,Grummt I,Misteli T

    更新日期：2008-05-23 00:00:00

  • Late S phase-specific recruitment of Mre11 complex triggers hierarchical assembly of telomere replication proteins in Saccharomyces cerevisiae.

    abstract：:In Saccharomyces cerevisiae, telomere replication occurs in late S phase and is accompanied by dynamic remodeling of its protein components. Here, we show that MRX (Mre11-Rad50-Xrs2), an evolutionarily conserved protein complex involved in DNA double-strand break (DSB) repair, is recruited to the telomeres in late S p...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2005.01.014

    authors： Takata H,Tanaka Y,Matsuura A

    更新日期：2005-02-18 00:00:00

  • Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein.

    abstract：:The adenomatous polyposis coli (APC) tumor-suppressor protein, together with Axin and GSK3beta, forms a Wnt-regulated signaling complex that mediates phosphorylation-dependent degradation of beta-catenin by the proteasome. Siah-1, the human homolog of Drosophila seven in absentia, is a p53-inducible mediator of cell c...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(01)00241-6

    authors： Liu J,Stevens J,Rote CA,Yost HJ,Hu Y,Neufeld KL,White RL,Matsunami N

    更新日期：2001-05-01 00:00:00

  • CRD-BP protects the coding region of betaTrCP1 mRNA from miR-183-mediated degradation.

    abstract：:miRNAs are largely known to base pair with the 3'UTR of target mRNAs, downregulating their stability and translation. mRNA of betaTrCP1 ubiquitin ligase is very unstable, but unlike the majority of mRNAs where 3'UTR determines the rate of mRNA turnover, betaTrCP1 mRNA contains cis-acting destabilizing elements within ...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2009.06.007

    authors： Elcheva I,Goswami S,Noubissi FK,Spiegelman VS

    更新日期：2009-07-31 00:00:00

  • Structural and functional organization of the Ska complex, a key component of the kinetochore-microtubule interface.

    abstract：:The Ska complex is an essential mitotic component required for accurate cell division in human cells. It is composed of three subunits that function together to establish stable kinetochore-microtubule interactions in concert with the Ndc80 network. We show that the structure of the Ska core complex is a W-shaped dime...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2012.03.005

    authors： Jeyaprakash AA,Santamaria A,Jayachandran U,Chan YW,Benda C,Nigg EA,Conti E

    更新日期：2012-05-11 00:00:00

  • Stress-induced map kinase Hog1 is part of transcription activation complexes.

    abstract：:In response to hyperosmotic environments, most eukaryotic cells activate a specialized mitogen-activated protein (MAP) kinase pathway. In S. cerevisiae, the key protein kinase, Hog1, coordinates the transcriptional induction of a variety of genes devoted to osmoadaptation and general stress protection. Depending on th...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(01)00221-0

    authors： Alepuz PM,Jovanovic A,Reiser V,Ammerer G

    更新日期：2001-04-01 00:00:00

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

    abstract：:The transition from transcription initiation to elongation at promoters of primary response genes (PRGs) in metazoan cells is controlled by inducible transcription factors, which utilize P-TEFb to phosphorylate RNA polymerase II (Pol II) in response to stimuli. Prior to stimulation, a fraction of P-TEFb is recruited t...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2015.11.004

    authors： McNamara RP,Reeder JE,McMillan EA,Bacon CW,McCann JL,D'Orso I

    更新日期：2016-01-07 00:00:00

  • Automated Structure- and Sequence-Based Design of Proteins for High Bacterial Expression and Stability.

    abstract：:Upon heterologous overexpression, many proteins misfold or aggregate, thus resulting in low functional yields. Human acetylcholinesterase (hAChE), an enzyme mediating synaptic transmission, is a typical case of a human protein that necessitates mammalian systems to obtain functional expression. We developed a computat...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2016.06.012

    authors： Goldenzweig A,Goldsmith M,Hill SE,Gertman O,Laurino P,Ashani Y,Dym O,Unger T,Albeck S,Prilusky J,Lieberman RL,Aharoni A,Silman I,Sussman JL,Tawfik DS,Fleishman SJ

    更新日期：2016-07-21 00:00:00

  • PML, SUMO, and RNF4: guardians of nuclear protein quality.

    abstract：:In this issue of Molecular Cell, Guo et al. (2014) report that misfolded or aggregated nuclear proteins, such as pathogenic polyQ proteins, are cleared by a SUMO-dependent quality control pathway, which involves the E3 SUMO ligase PML and the SUMO-targeted ubiquitin ligase RNF4. ...

    journal_title：Molecular cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.molcel.2014.06.022

    authors： Gärtner A,Muller S

    更新日期：2014-07-03 00:00:00

  • The mechanism of a neurotransmitter:sodium symporter--inward release of Na+ and substrate is triggered by substrate in a second binding site.

    abstract：:Eukaryotic neurotransmitter:sodium symporters (NSSs), targets for antidepressants and psychostimulants, terminate neurotransmission by sodium-driven reuptake. The crystal structure of LeuT(Aa), a prokaryotic NSS homolog, revealed an occluded state in which one leucine and two Na(+) ions are bound, but provided limited...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2008.05.008

    authors： Shi L,Quick M,Zhao Y,Weinstein H,Javitch JA

    更新日期：2008-06-20 00:00:00

  • Glucose-induced β-catenin acetylation enhances Wnt signaling in cancer.

    abstract：:Nuclear accumulation of β-catenin, a widely recognized marker of poor cancer prognosis, drives cancer cell proliferation and senescence bypass and regulates incretins, critical regulators of fat and glucose metabolism. Diabetes, characterized by elevated blood glucose levels, is associated with increased cancer risk, ...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2012.11.022

    authors： Chocarro-Calvo A,García-Martínez JM,Ardila-González S,De la Vieja A,García-Jiménez C

    更新日期：2013-02-07 00:00:00

  • Conserved GU-rich elements mediate mRNA decay by binding to CUG-binding protein 1.

    abstract：:We used computational algorithms to find conserved sequences in the 3' untranslated region (UTR) of transcripts that exhibited rapid decay in primary human T cells and found that the consensus sequence UGUUUGUUUGU, which we have termed a GU-rich element (GRE), was enriched in short-lived transcripts. Using a tet-off r...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2007.11.024

    authors： Vlasova IA,Tahoe NM,Fan D,Larsson O,Rattenbacher B,Sternjohn JR,Vasdewani J,Karypis G,Reilly CS,Bitterman PB,Bohjanen PR

    更新日期：2008-02-01 00:00:00

  • Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt.

    abstract：:Forkhead box O (FOXO) transcription factors, the key regulators of cell survival, are negatively controlled through the PI3K-Akt signaling pathway. Phosphorylation of FOXO by Akt leads to cytoplasmic localization and subsequent degradation via the ubiquitin-proteasome system. Here we show a paradigm of FOXO1 regulatio...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2008.09.013

    authors： Yamagata K,Daitoku H,Takahashi Y,Namiki K,Hisatake K,Kako K,Mukai H,Kasuya Y,Fukamizu A

    更新日期：2008-10-24 00:00:00

  • Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability.

    abstract：:RNA-binding proteins coordinate the fates of multiple RNAs, but the principles underlying these global interactions remain poorly understood. We elucidated regulatory mechanisms of the RNA-binding protein HuR, by integrating data from diverse high-throughput targeting technologies, specifically PAR-CLIP, RIP-chip, and...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2011.06.007

    authors： Mukherjee N,Corcoran DL,Nusbaum JD,Reid DW,Georgiev S,Hafner M,Ascano M Jr,Tuschl T,Ohler U,Keene JD

    更新日期：2011-08-05 00:00:00

  • Hierarchical regulation of WASP/WAVE proteins.

    abstract：:Members of the Wiskott-Aldrich syndrome protein (WASP) family control actin dynamics in eukaryotic cells by stimulating the actin nucleating activity of the Arp2/3 complex. The prevailing paradigm for WASP regulation invokes allosteric relief of autoinhibition by diverse upstream activators. Here we demonstrate an add...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2008.10.012

    authors： Padrick SB,Cheng HC,Ismail AM,Panchal SC,Doolittle LK,Kim S,Skehan BM,Umetani J,Brautigam CA,Leong JM,Rosen MK

    更新日期：2008-11-07 00:00:00

  • RAD51AP1 is a structure-specific DNA binding protein that stimulates joint molecule formation during RAD51-mediated homologous recombination.

    abstract：:Homologous recombination is essential for preserving genome integrity. Joining of homologous DNA molecules through strand exchange, a pivotal step in recombination, is mediated by RAD51. Here, we identify RAD51AP1 as a RAD51 accessory protein that specifically stimulates joint molecule formation through the combinatio...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2007.08.025

    authors： Modesti M,Budzowska M,Baldeyron C,Demmers JA,Ghirlando R,Kanaar R

    更新日期：2007-11-09 00:00:00

  • A peptide signal for adapter protein-mediated degradation by the AAA+ protease ClpCP.

    abstract：:ComS is an antiadaptor protein that binds to MecA, displacing the competence transcription factor ComK. This protects ComK from degradation by the ClpCP protease and turns on the switch leading to bistable gene expression. Here we identify the motifs on ComK and ComS that mediate binding to MecA, and we show that they...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2007.05.011

    authors： Prepiak P,Dubnau D

    更新日期：2007-06-08 00:00:00

  • DNA binding and bending to initiate packaging of phage lambda DNA.

    abstract：:Physical and genetic studies verify that the DNA binding domain of protein gpNu1 (which initiates packaging of phage lambda DNA) is a winged helix-turn-helix (w HTH) and that gpNu1 dimers bind sites that are brought close through DNA bending. ...

    journal_title：Molecular cell

    pub_type： 评论,杂志文章

    doi：10.1016/s1097-2765(02)00536-1

    authors： Campbell A

    更新日期：2002-05-01 00:00:00

  • Nuclear myosin VI enhances RNA polymerase II-dependent transcription.

    abstract：:Myosin VI is the only myosin that moves toward the minus end of actin filaments, suggesting a unique biological function. Here, we show that myosin VI is present in the nucleus of mammalian cells where it colocalizes with newly transcribed mRNA and with RNA polymerase II (RNAPII) and is detected in the RNAPII complex....

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2006.07.005

    authors： Vreugde S,Ferrai C,Miluzio A,Hauben E,Marchisio PC,Crippa MP,Bussi M,Biffo S

    更新日期：2006-09-01 00:00:00

  • Smad proteins bind a conserved RNA sequence to promote microRNA maturation by Drosha.

    abstract：:The signal transducers of the transforming growth factor beta (TGFbeta)/bone morphogenetic protein (BMP), the Smads, promote the expression of a subset of miRNAs by facilitating the cleavage reaction by Drosha. The mechanism that limits Smad-mediated processing to a selective group of miRNAs remained hitherto unexplor...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2010.07.011

    authors： Davis BN,Hilyard AC,Nguyen PH,Lagna G,Hata A

    更新日期：2010-08-13 00:00:00

  • Mouse Heterochromatin Adopts Digital Compaction States without Showing Hallmarks of HP1-Driven Liquid-Liquid Phase Separation.

    abstract：:The formation of silenced and condensed heterochromatin foci involves enrichment of heterochromatin protein 1 (HP1). HP1 can bridge chromatin segments and form liquid droplets, but the biophysical principles underlying heterochromatin compartmentalization in the cell nucleus are elusive. Here, we assess mechanisticall...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2020.02.005

    authors： Erdel F,Rademacher A,Vlijm R,Tünnermann J,Frank L,Weinmann R,Schweigert E,Yserentant K,Hummert J,Bauer C,Schumacher S,Al Alwash A,Normand C,Herten DP,Engelhardt J,Rippe K

    更新日期：2020-04-16 00:00:00

  • A critical role for noncoding 5S rRNA in regulating Mdmx stability.

    abstract：:Both p53 and Mdmx are ubiquitinated and degraded by the same E3 ligase Mdm2; interestingly, however, while p53 is rapidly degraded by Mdm2, Mdmx is a stable protein in most cancer cells. Thus, the mechanism by which Mdmx is degraded by Mdm2 needs further elucidation. Here, we identified the noncoding 5S rRNA as a majo...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2011.08.020

    authors： Li M,Gu W

    更新日期：2011-09-16 00:00:00

  • RNA Structure Switches RBP Binding.

    abstract：:RNA sequence motifs are not sufficient for association with RBPs. In this issue of Molecular Cell, Taliaferro et al. (2016) demonstrate that, other than sequence motif, RNA secondary structure plays a repressive role on RBP binding, both in vitro and in vivo. ...

    journal_title：Molecular cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.molcel.2016.10.006

    authors： Luo Z,Yang Q,Yang L

    更新日期：2016-10-20 00:00:00

  • A switch in mitotic histone H4 lysine 20 methylation status is linked to M phase defects upon loss of HCF-1.

    abstract：:The abundant chromatin-associated human factor HCF-1 is a heterodimeric complex of HCF-1N and HCF-1C subunits that are essential for two stages of the cell cycle. The HCF-1N subunit promotes G1 phase progression, whereas the HCF-1C subunit ensures proper cytokinesis at completion of M phase. How the HCF-1C subunit fun...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2004.06.008

    authors： Julien E,Herr W

    更新日期：2004-06-18 00:00:00

  • SR proteins function in coupling RNAP II transcription to pre-mRNA splicing.

    abstract：:Transcription and splicing are functionally coupled, resulting in highly efficient splicing of RNA polymerase II (RNAP II) transcripts. The mechanism involved in this coupling is not known. To identify potential coupling factors, we carried out a comprehensive proteomic analysis of immunopurified human RNAP II, identi...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2007.05.036

    authors： Das R,Yu J,Zhang Z,Gygi MP,Krainer AR,Gygi SP,Reed R

    更新日期：2007-06-22 00:00:00

  • Promoter Distortion and Opening in the RNA Polymerase II Cleft.

    abstract：:Transcription initiation requires opening of promoter DNA in the RNA polymerase II (Pol II) pre-initiation complex (PIC), but it remains unclear how this is achieved. Here we report the cryo-electron microscopic (cryo-EM) structure of a yeast PIC that contains underwound, distorted promoter DNA in the closed Pol II cl...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2018.10.014

    authors： Dienemann C,Schwalb B,Schilbach S,Cramer P

    更新日期：2019-01-03 00:00:00

  • RNase H and multiple RNA biogenesis factors cooperate to prevent RNA:DNA hybrids from generating genome instability.

    abstract：:Genome instability, a hallmark of cancer progression, is thought to arise through DNA double strand breaks (DSBs). Studies in yeast and mammalian cells have shown that DSBs and instability can occur through RNA:DNA hybrids generated by defects in RNA elongation and splicing. We report that in yeast hybrids naturally f...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2011.10.017

    authors： Wahba L,Amon JD,Koshland D,Vuica-Ross M

    更新日期：2011-12-23 00:00:00

  • Genomic Copy-Number Loss Is Rescued by Self-Limiting Production of DNA Circles.

    abstract：:Copy-number changes generate phenotypic variability in health and disease. Whether organisms protect against copy-number changes is largely unknown. Here, we show that Saccharomyces cerevisiae monitors the copy number of its ribosomal DNA (rDNA) and rapidly responds to copy-number loss with the clonal amplification of...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2018.08.036

    authors： Mansisidor A,Molinar T Jr,Srivastava P,Dartis DD,Pino Delgado A,Blitzblau HG,Klein H,Hochwagen A

    更新日期：2018-11-01 00:00:00