Identification of an mRNP complex regulating tumorigenesis at the translational elongation step.


:Transcript-selective translational regulation of epithelial-mesenchymal transition (EMT) by transforming growth factor-β (TGF-β) is directed by the hnRNP E1-containing TGF-β-activated-translational (BAT) mRNP complex. Herein, eukaryotic elongation factor-1 A1 (eEF1A1) is identified as an integral component of the BAT complex. Translational silencing of Dab2 and ILEI, two EMT transcripts, is mediated by the binding of hnRNP E1 and eEF1A1 to their 3'UTR BAT element, whereby hnRNP E1 stalls translational elongation by inhibiting the release of eEF1A1 from the ribosomal A site. TGF-β-mediated hnRNP E1 phosphorylation, through Akt2, disrupts the BAT complex, thereby restoring translation of target EMT transcripts. Attenuation of hnRNP E1 expression in two noninvasive breast epithelial cells (NMuMG and MCF-7) not only induced EMT but also enabled cells to form metastatic lesions in vivo. Thus, translational regulation by TGF-β at the elongation stage represents a critical checkpoint coordinating the expression of EMT transcripts required during development and in tumorigenesis and metastatic progression.


Mol Cell


Molecular cell


Hussey GS,Chaudhury A,Dawson AE,Lindner DJ,Knudsen CR,Wilce MC,Merrick WC,Howe PH




Has Abstract


2011-02-18 00:00:00














  • Structure and mechanism of RNA polymerase II CTD phosphatases.

    abstract::Recycling of RNA polymerase II (Pol II) after transcription requires dephosphorylation of the polymerase C-terminal domain (CTD) by the phosphatase Fcp1. We report the X-ray structure of the small CTD phosphatase Scp1, which is homologous to the Fcp1 catalytic domain. The structure shows a core fold and an active cent...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Kamenski T,Heilmeier S,Meinhart A,Cramer P

    更新日期:2004-08-13 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


    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

  • Features of ribosome-peptidyl-tRNA interactions essential for tryptophan induction of tna operon expression.

    abstract::Certain nascent peptide sequences, when within the ribosomal exit tunnel, can inhibit translation termination and/or peptide elongation. The 24 residue leader peptidyl-tRNA of the tna operon of E. coli, TnaC-tRNA(Pro), in the presence of excess tryptophan, resists cleavage at the tnaC stop codon. TnaC residue Trp12 is...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Cruz-Vera LR,Rajagopal S,Squires C,Yanofsky C

    更新日期:2005-08-05 00:00:00

  • Adaptation in CRISPR-Cas Systems.

    abstract::Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins constitute an adaptive immune system in prokaryotes. The system preserves memories of prior infections by integrating short segments of foreign DNA, termed spacers, into the CRISPR array in a process termed adaptati...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审


    authors: Sternberg SH,Richter H,Charpentier E,Qimron U

    更新日期:2016-03-17 00:00:00

  • Interleukin 2 receptors and detergent-resistant membrane domains define a clathrin-independent endocytic pathway.

    abstract::Clathrin-dependent endocytosis has long been presented as the only efficient mechanism by which transmembrane receptors are internalized. We selectively blocked this process using dominant-negative mutants of Eps15 and showed that clathrin-mediated endocytosis of transferrin was inhibited, while endocytosis of interle...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Lamaze C,Dujeancourt A,Baba T,Lo CG,Benmerah A,Dautry-Varsat A

    更新日期:2001-03-01 00:00:00

  • The effect of distance on long-range chromatin interactions.

    abstract::We have used gene competition to distinguish between possible mechanisms of transcriptional activation of the genes of the human beta-globin locus. The insertion of a second beta-globin gene at different points in the locus shows that the more proximal beta gene competes more effectively for activation by the locus co...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Dillon N,Trimborn T,Strouboulis J,Fraser P,Grosveld F

    更新日期:1997-12-01 00:00:00

  • Redox Control of Mitochondrial Calcium Uptake.

    abstract::Dong et al. (2017) establish how the mitochondrial Ca2+ uniporter (MCU) integrates Ca2+ and oxidative stress signals by identifying a cysteine residue that controls MCU channel activity, a mechanism causing mitochondrial Ca2+ overload and cell death during oxidative stress. ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Demaurex N,Rosselin M

    更新日期:2017-03-16 00:00:00

  • The survivin-like C. elegans BIR-1 protein acts with the Aurora-like kinase AIR-2 to affect chromosomes and the spindle midzone.

    abstract::Baculoviral IAP repeat proteins (BIRPs) may affect cell death, cell division, and tumorigenesis. The C. elegans BIRP BIR-1 was localized to chromosomes and to the spindle midzone. Embryos and fertilized oocytes lacking BIR-1 had defects in chromosome behavior, spindle midzone formation, and cytokinesis. We observed in...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Speliotes EK,Uren A,Vaux D,Horvitz HR

    更新日期:2000-08-01 00:00:00

  • UneCLIPsing HuR nuclear function.

    abstract::The RNA-binding protein HuR, while known to stabilize cytoplasmic mRNAs, is largely nuclear. In this issue of Molecular Cell, Mukherjee et al. (2011) and Lebedeva et al. (2011) identify transcriptome-wide HuR-RNA interactions using PAR-CLIP, unveiling HuR's nuclear role in pre-mRNA processing. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Srikantan S,Gorospe M

    更新日期:2011-08-05 00:00:00

  • Peptide-induced negative selection of thymocytes activates transcription of an NF-kappa B inhibitor.

    abstract::Negative selection eliminates thymocytes bearing autoreactive T cell receptors (TCR) via an apoptotic mechanism. We have cloned an inhibitor of NF-kappa B, I kappa BNS, which is rapidly expressed upon TCR-triggered but not dexamethasone- or gamma irradiation-stimulated thymocyte death. The predicted protein contains s...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Fiorini E,Schmitz I,Marissen WE,Osborn SL,Touma M,Sasada T,Reche PA,Tibaldi EV,Hussey RE,Kruisbeek AM,Reinherz EL,Clayton LK

    更新日期:2002-03-01 00:00:00

  • Chromatin remodeling in vivo: evidence for a nucleosome sliding mechanism.

    abstract::Members of the ISWI family of chromatin remodeling factors exhibit ATP-dependent nucleosome sliding, loading, and spacing activities in vitro. However, it is unclear which of these activities are utilized by ISWI complexes to remodel chromatin in vivo. We therefore sought to identify the mechanisms of chromatin remode...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Fazzio TG,Tsukiyama T

    更新日期:2003-11-01 00:00:00

  • Transcriptional regulation by p53 through intrinsic DNA/chromatin binding and site-directed cofactor recruitment.

    abstract::The tumor suppressor protein, p53, plays a critical role in mediating cellular response to stress signals by regulating genes involved in cell cycle arrest and apoptosis. p53 is believed to be inactive for DNA binding unless its C terminus is modified or structurally altered. We show that unmodified p53 actively binds...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Espinosa JM,Emerson BM

    更新日期:2001-07-01 00:00:00

  • Autodeubiquitination protects the tumor suppressor BAP1 from cytoplasmic sequestration mediated by the atypical ubiquitin ligase UBE2O.

    abstract::The tumor suppressor BAP1 interacts with chromatin-associated proteins and regulates cell proliferation, but its mechanism of action and regulation remain poorly defined. We show that the ubiquitin-conjugating enzyme UBE2O multi-monoubiquitinates the nuclear localization signal of BAP1, thereby inducing its cytoplasmi...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Mashtalir N,Daou S,Barbour H,Sen NN,Gagnon J,Hammond-Martel I,Dar HH,Therrien M,Affar el B

    更新日期:2014-05-08 00:00:00

  • Xist Deletional Analysis Reveals an Interdependency between Xist RNA and Polycomb Complexes for Spreading along the Inactive X.

    abstract::During X-inactivation, Xist RNA spreads along an entire chromosome to establish silencing. However, the mechanism and functional RNA elements involved in spreading remain undefined. By performing a comprehensive endogenous Xist deletion screen, we identify Repeat B as crucial for spreading Xist and maintaining Polycom...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Colognori D,Sunwoo H,Kriz AJ,Wang CY,Lee JT

    更新日期:2019-04-04 00:00:00

  • The structure of the bacteriophage PRD1 spike sheds light on the evolution of viral capsid architecture.

    abstract::Comparisons of bacteriophage PRD1 and adenovirus protein structures and virion architectures have been instrumental in unraveling an evolutionary relationship and have led to a proposal of a phylogeny-based virus classification. The structure of the PRD1 spike protein P5 provides further insight into the evolution of ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Merckel MC,Huiskonen JT,Bamford DH,Goldman A,Tuma R

    更新日期:2005-04-15 00:00:00

  • The structure of SOCS3 reveals the basis of the extended SH2 domain function and identifies an unstructured insertion that regulates stability.

    abstract::SOCS3 is essential for regulating the extent, duration, and specificity of cellular responses to cytokines such as G-CSF and IL-6. Here we describe the solution structure of SOCS3, the first structure determined for any SOCS protein, in complex with a phosphotyrosine-containing peptide from the IL-6 receptor signaling...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Babon JJ,McManus EJ,Yao S,DeSouza DP,Mielke LA,Sprigg NS,Willson TA,Hilton DJ,Nicola NA,Baca M,Nicholson SE,Norton RS

    更新日期:2006-04-21 00:00:00

  • The K48-K63 Branched Ubiquitin Chain Regulates NF-κB Signaling.

    abstract::Polyubiquitin chains of different topologies regulate diverse cellular processes. K48- and K63-linked chains, the two most abundant chain types, regulate proteolytic and signaling pathways, respectively. Although recent studies reported important roles for heterogeneous chains, the functions of branched ubiquitin chai...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Ohtake F,Saeki Y,Ishido S,Kanno J,Tanaka K

    更新日期:2016-10-20 00:00:00

  • Actin homolog MreB affects chromosome segregation by regulating topoisomerase IV in Escherichia coli.

    abstract::In Escherichia coli, topoisomerase IV, a type II topoisomerase, mediates the resolution of topological linkages between replicated daughter chromosomes and is essential for chromosome segregation. Topo IV activity is restricted to only a short interval late in the cell cycle. However, the mechanism that confers this t...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Madabhushi R,Marians KJ

    更新日期:2009-01-30 00:00:00

  • Multimodal activation of the ubiquitin ligase SCF by Nedd8 conjugation.

    abstract::Conjugation of ubiquitin-like protein Nedd8 to cullins (neddylation) is essential for the function of cullin-RING ubiquitin ligases (CRLs). Here, we show that neddylation stimulates CRL activity by multiple mechanisms. For the initiator ubiquitin, the major effect is to bridge the approximately 50 A gap between naked ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Saha A,Deshaies RJ

    更新日期:2008-10-10 00:00:00

  • Structural Basis for Guide RNA Processing and Seed-Dependent DNA Targeting by CRISPR-Cas12a.

    abstract::The CRISPR-associated protein Cas12a (Cpf1), which has been repurposed for genome editing, possesses two distinct nuclease activities: endoribonuclease activity for processing its own guide RNAs and RNA-guided DNase activity for target DNA cleavage. To elucidate the molecular basis of both activities, we determined cr...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Swarts DC,van der Oost J,Jinek M

    更新日期:2017-04-20 00:00:00

  • Control of actin turnover by a salmonella invasion protein.

    abstract::Salmonella force their way into nonphagocytic host intestinal cells to initiate infection. Uptake is triggered by delivery into the target cell of bacterial effector proteins that stimulate cytoskeletal rearrangements and membrane ruffling. The Salmonella invasion protein A (SipA) effector is an actin binding protein ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: McGhie EJ,Hayward RD,Koronakis V

    更新日期:2004-02-27 00:00:00

  • A DDX6-CNOT1 complex and W-binding pockets in CNOT9 reveal direct links between miRNA target recognition and silencing.

    abstract::CCR4-NOT is a major effector complex in miRNA-mediated gene silencing. It is recruited to miRNA targets through interactions with tryptophan (W)-containing motifs in TNRC6/GW182 proteins and is required for both translational repression and degradation of miRNA targets. Here, we elucidate the structural basis for the ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Chen Y,Boland A,Kuzuoğlu-Öztürk D,Bawankar P,Loh B,Chang CT,Weichenrieder O,Izaurralde E

    更新日期:2014-06-05 00:00:00

  • Transcriptional Bursting and Co-bursting Regulation by Steroid Hormone Release Pattern and Transcription Factor Mobility.

    abstract::Genes are transcribed in a discontinuous pattern referred to as RNA bursting, but the mechanisms regulating this process are unclear. Although many physiological signals, including glucocorticoid hormones, are pulsatile, the effects of transient stimulation on bursting are unknown. Here we characterize RNA synthesis f...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Stavreva DA,Garcia DA,Fettweis G,Gudla PR,Zaki GF,Soni V,McGowan A,Williams G,Huynh A,Palangat M,Schiltz RL,Johnson TA,Presman DM,Ferguson ML,Pegoraro G,Upadhyaya A,Hager GL

    更新日期:2019-09-19 00:00:00

  • pRB contains an E2F1-specific binding domain that allows E2F1-induced apoptosis to be regulated separately from other E2F activities.

    abstract::The interaction between pRB and E2F is critical for control of the cell cycle and apoptosis. Here we report that pRB contains two distinct E2F binding sites. The previously identified E2F binding site on pRB is necessary for stable association with E2Fs on DNA. A second E2F interaction site is located entirely within ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Dick FA,Dyson N

    更新日期:2003-09-01 00:00:00

  • Loss of Dynamic RNA Interaction and Aberrant Phase Separation Induced by Two Distinct Types of ALS/FTD-Linked FUS Mutations.

    abstract::FUS is a nuclear RNA-binding protein, and its cytoplasmic aggregation is a pathogenic signature of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). It remains unknown how the FUS-RNA interactions contribute to phase separation and whether its phase behavior is affected by ALS-linked mutations. He...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Niaki AG,Sarkar J,Cai X,Rhine K,Vidaurre V,Guy B,Hurst M,Lee JC,Koh HR,Guo L,Fare CM,Shorter J,Myong S

    更新日期:2020-01-02 00:00:00

  • WTX: an unexpected regulator for p53.

    abstract::The WTX gene is frequently lost or mutated in Wilms tumor. In this issue of Molecular Cell, Kim et al. (2012) identify WTX modulation of p53 tumor-suppressor activity through regulation of p53 acetylation. Therefore, WTX differentially regulates the oncogenic β-catenin pathway and the tumor-suppressing p53 pathway. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Dai C,Gu W

    更新日期:2012-03-09 00:00:00

  • Regulation of the histone H4 monomethylase PR-Set7 by CRL4(Cdt2)-mediated PCNA-dependent degradation during DNA damage.

    abstract::The histone methyltransferase PR-Set7/Set8 is the sole enzyme that catalyzes monomethylation of histone H4 at K20 (H4K20me1). Previous reports document disparate evidence regarding PR-Set7 expression during the cell cycle, the biological relevance of PR-Set7 interaction with PCNA, and its role in the cell. We find tha...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Oda H,Hübner MR,Beck DB,Vermeulen M,Hurwitz J,Spector DL,Reinberg D

    更新日期:2010-11-12 00:00:00

  • Integrating cardiac PIP3 and cAMP signaling through a PKA anchoring function of p110γ.

    abstract::Adrenergic stimulation of the heart engages cAMP and phosphoinositide second messenger signaling cascades. Cardiac phosphoinositide 3-kinase p110γ participates in these processes by sustaining β-adrenergic receptor internalization through its catalytic function and by controlling phosphodiesterase 3B (PDE3B) activity ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Perino A,Ghigo A,Ferrero E,Morello F,Santulli G,Baillie GS,Damilano F,Dunlop AJ,Pawson C,Walser R,Levi R,Altruda F,Silengo L,Langeberg LK,Neubauer G,Heymans S,Lembo G,Wymann MP,Wetzker R,Houslay MD,Iaccarino G,S

    更新日期:2011-04-08 00:00:00

  • Recognition of specific DNA sequences.

    abstract::Proteins that recognize specific DNA sequences play a central role in the regulation of transcription. The tremendous increase in structural information on protein-DNA complexes has uncovered a remarkable structural diversity in DNA binding folds, while at the same time revealing common themes in binding to target sit...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审


    authors: Garvie CW,Wolberger C

    更新日期:2001-11-01 00:00:00

  • RAD51AP1 Is an Essential Mediator of Alternative Lengthening of Telomeres.

    abstract::Alternative lengthening of telomeres (ALT) is a homology-directed repair (HDR) mechanism of telomere elongation that controls proliferation in aggressive cancers. We show that the disruption of RAD51-associated protein 1 (RAD51AP1) in ALT+ cancer cells leads to generational telomere shortening. This is due to RAD51AP1...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Barroso-González J,García-Expósito L,Hoang SM,Lynskey ML,Roncaioli JL,Ghosh A,Wallace CT,de Vitis M,Modesti M,Bernstein KA,Sarkar SN,Watkins SC,O'Sullivan RJ

    更新日期:2019-10-03 00:00:00