Mechanism of foreign DNA selection in a bacterial adaptive immune system.

abstract：:Protein function originates from a cooperation of structural rigidity, dynamics at different timescales, and allostery. However, how these three pillars of protein function are integrated is still only poorly understood. Here we show how these pillars are connected in Protein Tyrosine Phosphatase 1B (PTP1B), a drug ta...

journal_title：Molecular cell

authors： Choy MS,Li Y,Machado LESF,Kunze MBA,Connors CR,Wei X,Lindorff-Larsen K,Page R,Peti W

更新日期：2017-02-16 00:00:00

abstract：:Metformin has been reported to possess antitumor activity and maintain high cytotoxic T lymphocyte (CTL) immune surveillance. However, the functions and detailed mechanisms of metformin's role in cancer immunity are not fully understood. Here, we show that metformin increases CTL activity by reducing the stability and...

journal_title：Molecular cell

authors： Cha JH,Yang WH,Xia W,Wei Y,Chan LC,Lim SO,Li CW,Kim T,Chang SS,Lee HH,Hsu JL,Wang HL,Kuo CW,Chang WC,Hadad S,Purdie CA,McCoy AM,Cai S,Tu Y,Litton JK,Mittendorf EA,Moulder SL,Symmans WF,Thompson AM,Piwnica-

更新日期：2018-08-16 00:00:00

abstract：:Given the intimate link between inflammation and dysregulated cell proliferation in cancer, we investigated cytokine-triggered gene expression in different cell cycle stages. Transcriptome analysis revealed that G1 release through cyclin-dependent kinase 6 (CDK6) and CDK4 primes and cooperates with the cytokine-driven...

journal_title：Molecular cell

authors： Handschick K,Beuerlein K,Jurida L,Bartkuhn M,Müller H,Soelch J,Weber A,Dittrich-Breiholz O,Schneider H,Scharfe M,Jarek M,Stellzig J,Schmitz ML,Kracht M

更新日期：2014-01-23 00:00:00

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

authors： Li M,Gu W

更新日期：2011-09-16 00:00:00

abstract：:Interphase chromatin is organized into topologically associating domains (TADs). Within TADs, chromatin looping interactions are formed between DNA regulatory elements, but their functional importance for the establishment of the 3D genome organization and gene regulation during development is unclear. Using high-reso...

journal_title：Molecular cell

authors： Ogiyama Y,Schuettengruber B,Papadopoulos GL,Chang JM,Cavalli G

更新日期：2018-07-05 00:00:00

abstract：:Ubiquitin-mediated proteolysis regulates the activity of diverse receptor systems. Here, we identify Smurf2, a C2-WW-HECT domain ubiquitin ligase and show that Smurf2 associates constitutively with Smad7. Smurf2 is nuclear, but binding to Smad7 induces export and recruitment to the activated TGF beta receptor, where i...

journal_title：Molecular cell

authors： Kavsak P,Rasmussen RK,Causing CG,Bonni S,Zhu H,Thomsen GH,Wrana JL

更新日期：2000-12-01 00:00:00

abstract：:Budding yeast Cdc13, Stn1, and Ten1 form the CST complex to protect telomeres from lethal DNA degradation. It remains unknown whether similar complexes are conserved in higher eukaryotes or not. Here we isolated mammalian STN1 and TEN1 homologs and CTC1 (conserved telomere maintenance component 1). The three proteins ...

journal_title：Molecular cell

authors： Miyake Y,Nakamura M,Nabetani A,Shimamura S,Tamura M,Yonehara S,Saito M,Ishikawa F

更新日期：2009-10-23 00:00:00

abstract：:Two yeast enzymes that catalyze aminoacylation of tRNAs, MetRS and GluRS, form a complex with the protein Arc1p. We show here that association of Arc1p with MetRS and GluRS is required in vivo for effective recruitment of the corresponding cognate tRNAs within this complex. Arc1p is linked to MetRS and GluRS through i...

journal_title：Molecular cell

authors： Simos G,Sauer A,Fasiolo F,Hurt EC

更新日期：1998-01-01 00:00:00

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

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

abstract：:Aberrant folding and fibrillar aggregation by polyglutamine (polyQ) expansion proteins are associated with cytotoxicity in Huntington's disease and other neurodegenerative disorders. Hsp70 chaperones have an inhibitory effect on fibril formation and can alleviate polyQ cytotoxicity. Here we show that the cytosolic cha...

journal_title：Molecular cell

authors： Behrends C,Langer CA,Boteva R,Böttcher UM,Stemp MJ,Schaffar G,Rao BV,Giese A,Kretzschmar H,Siegers K,Hartl FU

更新日期：2006-09-15 00:00:00

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

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

更新日期：2017-04-20 00:00:00

abstract：:Group II intron RNPs are mobile genetic elements that attack and invade duplex DNA. In this work, we monitor the invasion reaction in vitro and establish a quantitative kinetic framework for the steps of this complex cascade. We find that target site specificity is achieved after DNA binding, which occurs nonspecifica...

journal_title：Molecular cell

authors： Aizawa Y,Xiang Q,Lambowitz AM,Pyle AM

更新日期：2003-03-01 00:00:00

abstract：:Replication forks frequently break and must be repaired by recombination. A reconstituted reaction now allows the factors that coordinate conversion from a recombination intermediate back to a replication fork to be defined. The PriA protein plays a key role in this control. ...

journal_title：Molecular cell

authors： Lovett ST

更新日期：2003-03-01 00:00:00

abstract：:TET proteins, by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are hypothesized, but not directly shown, to protect promoter CpG islands (CGIs) against abnormal DNA methylation (DNAm) in cancer. We define such a protective role linked to DNA damage from oxidative stress (OS) known to induce this...

journal_title：Molecular cell

authors： Zhang YW,Wang Z,Xie W,Cai Y,Xia L,Easwaran H,Luo J,Yen RC,Li Y,Baylin SB

更新日期：2017-01-19 00:00:00

abstract：:In this issue of Molecular Cell, Yang et al. (2011) demonstrate that Aurora B phosphorylates ATM, leading to its mitotic activation and ability to phosphorylate Bub1 and regulate the spindle checkpoint, thus maintaining genomic integrity. ...

journal_title：Molecular cell

authors： Bihani T,Hinds PW

更新日期：2011-11-18 00:00:00

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

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

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

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

更新日期：2011-02-04 00:00:00

abstract：:Gene-targeted knockout mice have been generated lacking the major uracil-DNA glycosylase, UNG. In contrast to ung- mutants of bacteria and yeast, such mice do not exhibit a greatly increased spontaneous mutation frequency. However, there is only slow removal of uracil from misincorporated dUMP in isolated ung-/- nucle...

journal_title：Molecular cell

authors： Nilsen H,Rosewell I,Robins P,Skjelbred CF,Andersen S,Slupphaug G,Daly G,Krokan HE,Lindahl T,Barnes DE

更新日期：2000-06-01 00:00:00

abstract：:Conjugation of ubiquitin (Ub) to a protein substrate targets the substrate for degradation or functional modification, which is tightly controlled by diverse mechanisms including phosphorylation of the substrate. An emerging mechanism involves regulation of the E3 Ub ligase, for example, the JNK-dependent phosphorylat...

journal_title：Molecular cell

authors： Yang C,Zhou W,Jeon MS,Demydenko D,Harada Y,Zhou H,Liu YC

更新日期：2006-01-06 00:00:00

abstract：:The inner nuclear membrane (INM) is continuous with the endoplasmic reticulum (ER) but harbors a distinctive proteome essential for nuclear functions. In yeast, the Asi1/Asi2/Asi3 ubiquitin ligase complex safeguards the INM proteome through the clearance of mislocalized ER membrane proteins. How the Asi complex select...

journal_title：Molecular cell

authors： Natarajan N,Foresti O,Wendrich K,Stein A,Carvalho P

更新日期：2020-01-02 00:00:00

abstract：:Floral transition in plants is regulated by an integrated network of flowering genetic pathways. We show that an Arabidopsis PIN1-type parvulin 1, Pin1At, controls floral transition by accelerating cis/trans isomerization of the phosphorylated Ser/Thr-Pro motifs in two MADS-domain transcription factors, SUPPRESSOR OF ...

journal_title：Molecular cell

authors： Wang Y,Liu C,Yang D,Yu H,Liou YC

更新日期：2010-01-15 00:00:00

abstract：:Ubiquitin-dependent proteolysis is an important mechanism that suppresses the beta-catenin transcription factor in cells without Wnt stimulation. A critical step in this regulatory pathway is to create a SCF(beta-TrCP) E3 ubiquitin ligase binding site for beta-catenin. Here we show that the SCF(beta-TrCP) binding site...

journal_title：Molecular cell

authors： Su Y,Fu C,Ishikawa S,Stella A,Kojima M,Shitoh K,Schreiber EM,Day BW,Liu B

更新日期：2008-12-05 00:00:00

abstract：:A variety of small RNAs, including the Dicer-dependent miRNAs and the Dicer-independent Piwi-interacting RNAs, associate with Argonaute family proteins to regulate gene expression in diverse cellular processes. These two species of small RNA have not been found in fungi. Here, by analyzing small RNAs associated with t...

journal_title：Molecular cell

authors： Lee HC,Li L,Gu W,Xue Z,Crosthwaite SK,Pertsemlidis A,Lewis ZA,Freitag M,Selker EU,Mello CC,Liu Y

更新日期：2010-06-25 00:00:00

abstract：:Phase-separated states of proteins underlie ribonucleoprotein (RNP) granules and nuclear RNA-binding protein assemblies that may nucleate protein inclusions associated with neurodegenerative diseases. We report that the N-terminal low-complexity domain of the RNA-binding protein Fused in Sarcoma (FUS LC) is structural...

journal_title：Molecular cell

authors： Burke KA,Janke AM,Rhine CL,Fawzi NL

更新日期：2015-10-15 00:00:00

abstract：:Although DNA looping between the initiator binding sites (iterons) of the replication origin (ori) of a plasmid and the iterons located in a cis-acting control sequence called inc has been postulated to promote negative control of plasmid DNA replication, not only was definitive evidence for such looping lacking, but ...

journal_title：Molecular cell

authors： Zzaman S,Bastia D

更新日期：2005-12-22 00:00:00

abstract：:The Wnt3a/β-catenin and Activin/SMAD2,3 signaling pathways synergize to induce endodermal differentiation of human embryonic stem cells; however, the underlying mechanism is not well understood. Using ChIP-seq and GRO-seq analyses, we show here that Wnt3a-induced β-catenin:LEF-1 enhancers recruit cohesin to direct enh...

journal_title：Molecular cell

authors： Estarás C,Benner C,Jones KA

更新日期：2015-06-04 00:00:00

abstract：:Regulatory sequences or erroneous incorporations during DNA transcription cause RNA polymerase backtracking and inactivation in all kingdoms of life. Reactivation requires RNA transcript cleavage. Essential transcription factors (GreA and GreB, or TFIIS) accelerate this reaction. We report four cryo-EM reconstructions...

journal_title：Molecular cell

authors： Abdelkareem M,Saint-André C,Takacs M,Papai G,Crucifix C,Guo X,Ortiz J,Weixlbaumer A

更新日期：2019-07-25 00:00:00

abstract：:The SMN complex assembles Sm cores on snRNAs, a key step in the biogenesis of snRNPs, the spliceosome's major components. Here, using SMN complex inhibitors identified by high-throughput screening and a ribo-proteomic strategy on formaldehyde crosslinked RNPs, we dissected this pathway in cells. We show that protein s...

journal_title：Molecular cell

authors： Yong J,Kasim M,Bachorik JL,Wan L,Dreyfuss G

更新日期：2010-05-28 00:00:00

abstract：:Type II topoisomerases are essential for resolving topologically entwined double-stranded DNA. Although anti-topoisomerase 2 (Top2) drugs are clinically important antibiotics and chemotherapies, to our knowledge, the mechanisms of cell killing by Top2 depletion and inactivation have never been directly compared. We sh...

journal_title：Molecular cell

authors： Baxter J,Diffley JF

更新日期：2008-06-20 00:00:00

abstract：:The Drosophila gene vasa (vas) encodes an RNA-binding protein required for embryonic patterning and germ cell specification. In vas mutants, translation of several germline mRNAs is reduced. Here we show that VAS interacts directly with the Drosophila homolog of yeast translation initiation factor 2, encoded by a nove...

journal_title：Molecular cell

authors： Carrera P,Johnstone O,Nakamura A,Casanova J,Jäckle H,Lasko P

更新日期：2000-01-01 00:00:00