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














  • Nek1 Regulates Rad54 to Orchestrate Homologous Recombination and Replication Fork Stability.

    abstract::Never-in-mitosis A-related kinase 1 (Nek1) has established roles in apoptosis and cell cycle regulation. We show that human Nek1 regulates homologous recombination (HR) by phosphorylating Rad54 at Ser572 in late G2 phase. Nek1 deficiency as well as expression of unphosphorylatable Rad54 (Rad54-S572A) cause unresolved ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Spies J,Waizenegger A,Barton O,Sürder M,Wright WD,Heyer WD,Löbrich M

    更新日期:2016-06-16 00:00:00

  • The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulates Autophagy by Controlling the Trafficking of the PtdIns(4)P Phosphatase SAC1.

    abstract::TMEM39A, encoding an ER-localized transmembrane protein, is a susceptibility locus for multiple autoimmune diseases. The molecular function of TMEM39A remains completely unknown. Here we demonstrated that TMEM39A, also called SUSR2, modulates autophagy activity by regulating the spatial distribution and levels of PtdI...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Miao G,Zhang Y,Chen D,Zhang H

    更新日期:2020-02-06 00:00:00

  • A BLAST from the past: ancient origin of human Sm proteins.

    abstract::In this issue of Molecular Cell, Zhang et al. and Møller et al. independently report studies of the E. coli Hfq protein, revealing significant sequence similarities with human Sm proteins. Their findings suggest that Hfq, and the Sm and Sm-like (Lsm) proteins, may function in stabilizing interactions between RNA molec...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Donahue WF,Jarrell KA

    更新日期:2002-01-01 00:00:00

  • Insights into FlaI functions in archaeal motor assembly and motility from structures, conformations, and genetics.

    abstract::Superfamily ATPases in type IV pili, type 2 secretion, and archaella (formerly archaeal flagella) employ similar sequences for distinct biological processes. Here, we structurally and functionally characterize prototypical superfamily ATPase FlaI in Sulfolobus acidocaldarius, showing FlaI activities in archaeal swimmi...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Reindl S,Ghosh A,Williams GJ,Lassak K,Neiner T,Henche AL,Albers SV,Tainer JA

    更新日期:2013-03-28 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


    authors: Julien E,Herr W

    更新日期:2004-06-18 00:00:00

  • Context-specific regulation of NF-κB target gene expression by EZH2 in breast cancers.

    abstract::Both EZH2 and NF-κB contribute to aggressive breast cancer, yet whether the two oncogenic factors have functional crosstalk in breast cancer is unknown. Here, we uncover an unexpected role of EZH2 in conferring the constitutive activation of NF-κB target gene expression in ER-negative basal-like breast cancer cells. T...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Lee ST,Li Z,Wu Z,Aau M,Guan P,Karuturi RK,Liou YC,Yu Q

    更新日期:2011-09-02 00:00:00

  • CENP-A targeting moves a step back.

    abstract::In a recent issue of Molecular Cell, Pidoux et al. (2009) and Williams et al. (2009) identify S. pombe Scm3 as the proximate factor in the Cnp1/CENP-A deposition pathway, providing a direct connection to centromere-localized Mis16-Mis18. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Baker RE

    更新日期:2009-02-27 00:00:00

  • Propagating prions in fungi and mammals.

    abstract::Prions constitute a rare class of protein, which can switch to a robust amyloid form and then propagate that form in the absence of a nucleic acid determinant, thereby creating a unique, protein-only infectious agent. Details of the mechanism that drives conversion to the prion form and then subsequent propagation of ...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审


    authors: Tuite MF,Koloteva-Levin N

    更新日期:2004-06-04 00:00:00

  • β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4.

    abstract::β-hydroxybutyrate (β-HB) elevation during fasting or caloric restriction is believed to induce anti-aging effects and alleviate aging-related neurodegeneration. However, whether β-HB alters the senescence pathway in vascular cells remains unknown. Here we report that β-HB promotes vascular cell quiescence, which signi...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Han YM,Bedarida T,Ding Y,Somba BK,Lu Q,Wang Q,Song P,Zou MH

    更新日期:2018-09-20 00:00:00

  • Cooperative activation of PI3K by Ras and Rho family small GTPases.

    abstract::Phosphoinositide 3-kinases (PI3Ks) and Ras and Rho family small GTPases are key regulators of cell polarization, motility, and chemotaxis. They influence each other's activities by direct and indirect feedback processes that are only partially understood. Here, we show that 21 small GTPase homologs activate PI3K. Usin...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Yang HW,Shin MG,Lee S,Kim JR,Park WS,Cho KH,Meyer T,Heo WD

    更新日期:2012-07-27 00:00:00

  • E1 on the move.

    abstract::E1 enzymes activate ubiquitin or related proteins and pass them to E2 enzymes. A recent structure and associated biochemical studies (Huang et al., 2005) show how an E1 binds its cognate E2 and indicates that large, conformational changes will be an integral component of the E1 reaction cycle. ...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审


    authors: VanDemark AP,Hill CP

    更新日期:2005-02-18 00:00:00

  • AMPK phosphorylation of raptor mediates a metabolic checkpoint.

    abstract::AMPK is a highly conserved sensor of cellular energy status that is activated under conditions of low intracellular ATP. AMPK responds to energy stress by suppressing cell growth and biosynthetic processes, in part through its inhibition of the rapamycin-sensitive mTOR (mTORC1) pathway. AMPK phosphorylation of the TSC...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Gwinn DM,Shackelford DB,Egan DF,Mihaylova MM,Mery A,Vasquez DS,Turk BE,Shaw RJ

    更新日期:2008-04-25 00:00:00

  • Regulated Proteolysis of MutSγ Controls Meiotic Crossing Over.

    abstract::Crossover recombination is essential for accurate chromosome segregation during meiosis. The MutSγ complex, Msh4-Msh5, facilitates crossing over by binding and stabilizing nascent recombination intermediates. We show that these activities are governed by regulated proteolysis. MutSγ is initially inactive for crossing ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: He W,Rao HBDP,Tang S,Bhagwat N,Kulkarni DS,Ma Y,Chang MAW,Hall C,Bragg JW,Manasca HS,Baker C,Verhees GF,Ranjha L,Chen X,Hollingsworth NM,Cejka P,Hunter N

    更新日期:2020-04-02 00:00:00

  • Changing of the guard: how ATM hands off DNA double-strand break signaling to ATR.

    abstract::In a recent issue of Molecular Cell, Shiotani and Zou (2009) elucidate the biochemical mechanism underlying sequential ATM and ATR activation at DNA double-strand breaks, demonstrating that resection transforms ATM substrates into ATR substrates. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Rhind N

    更新日期:2009-03-27 00:00:00

  • Bidirectional Transcription Arises from Two Distinct Hubs of Transcription Factor Binding and Active Chromatin.

    abstract::Anti-sense transcription originating upstream of mammalian protein-coding genes is a well-documented phenomenon, but remarkably little is known about the regulation or function of anti-sense promoters and the non-coding RNAs they generate. Here we define at nucleotide resolution the divergent transcription start sites...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Scruggs BS,Gilchrist DA,Nechaev S,Muse GW,Burkholder A,Fargo DC,Adelman K

    更新日期:2015-06-18 00:00:00

  • A Regulatory Module Controlling Homeostasis of a Plant Immune Kinase.

    abstract::Plant pattern recognition receptors (PRRs) perceive microbial and endogenous molecular patterns to activate immune signaling. The cytoplasmic kinase BIK1 acts downstream of multiple PRRs as a rate-limiting component, whose phosphorylation and accumulation are central to immune signal propagation. Previous work identif...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Wang J,Grubb LE,Wang J,Liang X,Li L,Gao C,Ma M,Feng F,Li M,Li L,Zhang X,Yu F,Xie Q,Chen S,Zipfel C,Monaghan J,Zhou JM

    更新日期:2018-02-01 00:00:00

  • The Biogenesis, Functions, and Challenges of Circular RNAs.

    abstract::Covalently closed circular RNAs (circRNAs) are produced by precursor mRNA back-splicing of exons of thousands of genes in eukaryotes. circRNAs are generally expressed at low levels and often exhibit cell-type-specific and tissue-specific patterns. Recent studies have shown that their biogenesis requires spliceosomal m...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审


    authors: Li X,Yang L,Chen LL

    更新日期:2018-08-02 00:00:00

  • Stay close to your sister.

    abstract::Yeast Sir2 protein regulates chromatin structure and suppresses recombination at the multiple tandem rDNA array. In the current issue of Cell, Kobayashi and colleagues reinvestigate rDNA dynamics in sir2 strains and find that Sir2 is necessary to recruit cohesins to the array, which influences the nature of rDNA recom...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审


    authors: Reid RJ,Rothstein R

    更新日期:2004-05-21 00:00:00

  • A hedgehog-insensitive form of patched provides evidence for direct long-range morphogen activity of sonic hedgehog in the neural tube.

    abstract::Cell pattern in the ventral neural tube is organized by Sonic hedgehog (Shh) secreted by floor plate cells. To assay the range of direct Shh action, we developed a general method for blocking transduction of Hedgehog (Hh) signals through ectopic expression of a deleted form of the Hh receptor Patched (Ptc), termed Ptc...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Briscoe J,Chen Y,Jessell TM,Struhl G

    更新日期:2001-06-01 00:00:00

  • Hsp90-dependent activation of protein kinases is regulated by chaperone-targeted dephosphorylation of Cdc37.

    abstract::Activation of protein kinase clients by the Hsp90 system is mediated by the cochaperone protein Cdc37. Cdc37 requires phosphorylation at Ser13, but little is known about the regulation of this essential posttranslational modification. We show that Ser13 of uncomplexed Cdc37 is phosphorylated in vivo, as well as in bin...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Vaughan CK,Mollapour M,Smith JR,Truman A,Hu B,Good VM,Panaretou B,Neckers L,Clarke PA,Workman P,Piper PW,Prodromou C,Pearl LH

    更新日期:2008-09-26 00:00:00

  • General and versatile autoinhibition of PLC isozymes.

    abstract::Phospholipase C (PLC) isozymes are directly activated by heterotrimeric G proteins and Ras-like GTPases to hydrolyze phosphatidylinositol 4,5-bisphosphate into the second messengers diacylglycerol and inositol 1,4,5-trisphosphate. Although PLCs play central roles in myriad signaling cascades, the molecular details of ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Hicks SN,Jezyk MR,Gershburg S,Seifert JP,Harden TK,Sondek J

    更新日期:2008-08-08 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

  • Crystal structure of Hck in complex with a Src family-selective tyrosine kinase inhibitor.

    abstract::The crystal structure of the autoinhibited form of Hck has been determined at 2.0 A resolution, in complex with a specific pyrazolo pyrimidine-type inhibitor, PP1. The activation segment, a key regulatory component of the catalytic domain, is unphosphorylated and is visualized in its entirety. Tyr-416, the site of act...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Schindler T,Sicheri F,Pico A,Gazit A,Levitzki A,Kuriyan J

    更新日期:1999-05-01 00:00:00

  • Allosteric control of ligand selectivity between estrogen receptors alpha and beta: implications for other nuclear receptors.

    abstract::Allosteric communication between interacting molecules is fundamental to signal transduction and many other cellular processes. To better understand the relationship between nuclear receptor (NR) ligand positioning and the formation of the coactivator binding pocket, we investigated the determinants of ligand selectiv...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Nettles KW,Sun J,Radek JT,Sheng S,Rodriguez AL,Katzenellenbogen JA,Katzenellenbogen BS,Greene GL

    更新日期:2004-02-13 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


    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

  • Oncogenic Ras and Akt signaling contribute to glioblastoma formation by differential recruitment of existing mRNAs to polysomes.

    abstract::In order to determine the global effects of oncogenic Ras and Akt signaling pathways on translational efficiencies, we compared the gene expression profiles of total cellular mRNA and mRNA associated with polysomes. We found that the immediate effect of Ras and Akt signaling blockade on transcription was relatively mo...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Rajasekhar VK,Viale A,Socci ND,Wiedmann M,Hu X,Holland EC

    更新日期:2003-10-01 00:00:00

  • Human Condensin I and II Drive Extensive ATP-Dependent Compaction of Nucleosome-Bound DNA.

    abstract::Structural maintenance of chromosomes (SMC) complexes are essential for genome organization from bacteria to humans, but their mechanisms of action remain poorly understood. Here, we characterize human SMC complexes condensin I and II and unveil the architecture of the human condensin II complex, revealing two putativ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Kong M,Cutts EE,Pan D,Beuron F,Kaliyappan T,Xue C,Morris EP,Musacchio A,Vannini A,Greene EC

    更新日期:2020-07-02 00:00:00

  • Cdh1 is a HECT of an activator.

    abstract::Cdh1 is a well-established activator of APC/C, a RING-type ubiquitin ligase. In this issue of Molecular Cell, Wan et al. (2011) report an APC/C-independent role of Cdh1 during development as an activator for Smurf1, a HECT-type ubiquitin ligase. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Jia L,Yu H

    更新日期:2011-12-09 00:00:00

  • An acid test for g proteins.

    abstract::In this issue, Isom et al. (2013) report their exciting discovery that G proteins can sense pH changes to fine-tune signaling in response to metabolic changes. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Sprang SR

    更新日期:2013-08-22 00:00:00

  • Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC.

    abstract::Gene expression mediated by viral vectors is subject to cell-to-cell variability, which limits the accuracy of gene delivery. When coupled with single-cell measurements, however, such variability provides an efficient means to quantify signaling dynamics in mammalian cells. Here, we illustrate the utility of this appr...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Wong JV,Yao G,Nevins JR,You L

    更新日期:2011-02-04 00:00:00