Partitioning of Chemotherapeutics into Nuclear Condensates-Opening the Door to New Approaches for Drug Development.

abstract：:The Polycomb repressive complex 2 (PRC2) confers transcriptional repression through histone H3 lysine 27 trimethylation (H3K27me3). Here, we examined how PRC2 is modulated by histone modifications associated with transcriptionally active chromatin. We provide the molecular basis of histone H3 N terminus recognition by...

journal_title：Molecular cell

authors： Schmitges FW,Prusty AB,Faty M,Stützer A,Lingaraju GM,Aiwazian J,Sack R,Hess D,Li L,Zhou S,Bunker RD,Wirth U,Bouwmeester T,Bauer A,Ly-Hartig N,Zhao K,Chan H,Gu J,Gut H,Fischle W,Müller J,Thomä NH

更新日期：2011-05-06 00:00:00

abstract：:Autophagy, a catabolic pathway that delivers cellular components to lysosomes for degradation, can be activated by stressful conditions such as nutrient starvation and endoplasmic reticulum (ER) stress. We report that thapsigargin, an ER stressor widely used to induce autophagy, in fact blocks autophagy. Thapsigargin ...

journal_title：Molecular cell

authors： Ganley IG,Wong PM,Gammoh N,Jiang X

更新日期：2011-06-24 00:00:00

abstract：:Eukaryotic transcription and mRNA processing depend upon the coordinated interactions of many proteins, including Spn1 and Spt6, which are conserved across eukaryotes, are essential for viability, and associate with each other in some of their biologically important contexts. Here we report crystal structures of the S...

journal_title：Molecular cell

authors： McDonald SM,Close D,Xin H,Formosa T,Hill CP

更新日期：2010-12-10 00:00:00

abstract：:Metazoan spliceosomes exhibit an elaborate protein composition required for canonical and alternative splicing. Thus, the minimal set of proteins essential for activation and catalysis remains elusive. We therefore purified in vitro assembled, precatalytic spliceosomal complex B, activated B(act), and step 1 complex C...

journal_title：Molecular cell

authors： Fabrizio P,Dannenberg J,Dube P,Kastner B,Stark H,Urlaub H,Lührmann R

更新日期：2009-11-25 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：:Heterochromatin is refractory to DNA transactions, including repair. In a recent issue of Molecular Cell, Goodarzi et al. (2008) reveal how the central transducing kinase of the DNA damage response relieves this natural barrier by increasing heterochromatic DNA accessibility. ...

journal_title：Molecular cell

authors： Fernandez-Capetillo O,Nussenzweig A

更新日期：2008-08-08 00:00:00

abstract：:Long DNA palindromes are sites of genome instability (deletions, amplification, and translocations) in both prokaryotic and eukaryotic cells. In Escherichia coli, genetic evidence has suggested that they are sites of DNA cleavage by the SbcCD complex that can be repaired by homologous recombination. Here we obtain in ...

journal_title：Molecular cell

authors： Eykelenboom JK,Blackwood JK,Okely E,Leach DR

更新日期：2008-03-14 00:00:00

abstract：:The circadian clock is a self-sustaining oscillator that controls daily rhythms. For the proper circadian gene expression, dynamic changes in chromatin structure are important. Although chromatin modifiers have been shown to play a role in circadian gene expression, the in vivo role of circadian signal-modulated chrom...

journal_title：Molecular cell

authors： Nam HJ,Boo K,Kim D,Han DH,Choe HK,Kim CR,Sun W,Kim H,Kim K,Lee H,Metzger E,Schuele R,Yoo SH,Takahashi JS,Cho S,Son GH,Baek SH

更新日期：2014-03-06 00:00:00

abstract：:Kong et al. (2020) present the low-resolution structure of the ATPɣS-bound human condensin I and II complexes and demonstrate that human condensins can extrude DNA loops in a symmetric and asymmetric fashion and compact nucleosome-bound DNA. ...

journal_title：Molecular cell

authors： Goloborodko A

更新日期：2020-07-02 00:00:00

abstract：:Viral initiators perform multiple functions in initiation of DNA replication including ori binding, melting, and unwinding, culminating in the formation of a double hexameric (DH) helicase. We have recapitulated the assembly of the papillomavirus E1 initiator DH helicase, providing the first description of how such a ...

journal_title：Molecular cell

authors： Schuck S,Stenlund A

更新日期：2005-11-11 00:00:00

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

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

更新日期：1997-12-01 00:00:00

abstract：:Networks of protein interactions coordinate cellular functions. We describe a bimolecular fluorescence complementation (BiFC) assay for determination of the locations of protein interactions in living cells. This approach is based on complementation between two nonfluorescent fragments of the yellow fluorescent protei...

journal_title：Molecular cell

authors： Hu CD,Chinenov Y,Kerppola TK

更新日期：2002-04-01 00:00:00

abstract：:Immune cell function depends on specific metabolic programs dictated by mitochondria, including nutrient oxidation, macromolecule synthesis, and post-translational modifications. Mitochondrial adaptations have been linked to acute and chronic inflammation, but the metabolic cues and precise mechanisms remain unclear. ...

journal_title：Molecular cell

authors： Chi Z,Chen S,Xu T,Zhen W,Yu W,Jiang D,Guo X,Wang Z,Zhang K,Li M,Zhang J,Fang H,Yang D,Ye Q,Yang X,Lin H,Yang F,Zhang X,Wang D

更新日期：2020-10-01 00:00:00

abstract：:Checkpoint proteins respond to DNA damage by halting the cell cycle until the damage is repaired. In this issue of Molecular Cell, Furuya et al. (2010) provide evidence that checkpoint proteins need to be removed from sites of damage in order to properly repair it. ...

journal_title：Molecular cell

authors： Paek AL,Weinert T

更新日期：2010-11-24 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：:Three introns whose splicing is activated during meiosis in S. cerevisiae contain a Mer1p-dependent splicing enhancer. The enhancer can impose Mer1p-activated splicing upon the constitutively spliced actin intron provided the basal splicing efficiency of actin is first reduced. Of several nonessential splicing factors...

journal_title：Molecular cell

authors： Spingola M,Ares M Jr

更新日期：2000-08-01 00:00:00

abstract：:In this issue of Molecular Cell, Dango and Mosammaparast discover that the human oxidative demethylase ALKBH3 functions in complex with a DNA helicase to eliminate N3-methylcytosine lesions from ssDNA and that specific cancer cell lines are dependent on this activity for proliferation (Dango et al., 2011). ...

journal_title：Molecular cell

authors： Camps M,Eichman BF

更新日期：2011-11-04 00:00:00

abstract：:In this issue, Takahara and Maeda (2012) discover that together, Pbp1 and sequestration of the TORC1 complex in cytoplasmic mRNP stress granules provides a negative regulatory mechanism for TORC1 signaling during stress. ...

journal_title：Molecular cell

authors： Buchan JR,Capaldi AP,Parker R

更新日期：2012-07-27 00:00:00

abstract：:A variety of debilitating diseases including diabetes, Alzheimer's, Huntington's, Parkinson's, and prion-based diseases are linked to stress within the endoplasmic reticulum (ER). Using S. cerevisiae, we sought to determine the relationship between protein misfolding, ER stress, and cell death. In the absence of ERV29...

journal_title：Molecular cell

authors： Haynes CM,Titus EA,Cooper AA

更新日期：2004-09-10 00:00:00

abstract：:BRCA1 and BRCA2 account for most cases of familial, early onset breast and/or ovarian cancer and encode products that each interact with hRAD51. Results presented here show that BRCA1 and BRCA2 coexist in a biochemical complex and colocalize in subnuclear foci in somatic cells and on the axial elements of developing s...

journal_title：Molecular cell

authors： Chen J,Silver DP,Walpita D,Cantor SB,Gazdar AF,Tomlinson G,Couch FJ,Weber BL,Ashley T,Livingston DM,Scully R

更新日期：1998-09-01 00:00:00

abstract：:Homeothermic organisms maintain their core body temperature in a narrow, tightly controlled range. Whether and how subtle circadian oscillations or disease-associated changes in core body temperature are sensed and integrated in gene expression programs remain elusive. Furthermore, a thermo-sensor capable of sensing t...

journal_title：Molecular cell

authors： Haltenhof T,Kotte A,De Bortoli F,Schiefer S,Meinke S,Emmerichs AK,Petermann KK,Timmermann B,Imhof P,Franz A,Loll B,Wahl MC,Preußner M,Heyd F

更新日期：2020-04-02 00:00:00

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：:Stalled replication forks are a critical problem for the cell because they can lead to complex genome rearrangements that underlie cell death and disease. Processes such as DNA damage tolerance and replication fork reversal protect stalled forks from these events. A central mediator of these DNA damage responses in hu...

journal_title：Molecular cell

authors： Kile AC,Chavez DA,Bacal J,Eldirany S,Korzhnev DM,Bezsonova I,Eichman BF,Cimprich KA

更新日期：2015-06-18 00:00:00

abstract：:Nup98 is a component of the nuclear pore that plays its primary role in the export of RNAs. Nup98 is expressed in two forms, derived from alternate mRNA splicing. Both forms are processed into two peptides through autoproteolysis mediated by the C-terminal domain of hNup98. The three-dimensional structure of the C-ter...

journal_title：Molecular cell

authors： Hodel AE,Hodel MR,Griffis ER,Hennig KA,Ratner GA,Xu S,Powers MA

更新日期：2002-08-01 00:00:00

abstract：:Organisms must survive a variety of stressful conditions, including sudden temperature increases that damage important cellular structures and interfere with essential functions. In response to heat stress, cells activate an ancient signaling pathway leading to the transient expression of heat shock or heat stress pro...

journal_title：Molecular cell

authors： Richter K,Haslbeck M,Buchner J

更新日期：2010-10-22 00:00:00

abstract：:In the death receptor induced apoptotic pathway, caspase-8 autocatalytically cleaves itself at specific cleavage sites. To better understand the regulatory mechanisms behind caspase-8 activation, we compared active wild-type caspase-8 (wtC8) and an uncleavable form of procaspase-8 (uncleavable C8). We demonstrate that...

journal_title：Molecular cell

authors： Donepudi M,Mac Sweeney A,Briand C,Grütter MG

更新日期：2003-02-01 00:00:00

abstract：:Brr2 is a unique DExD/H box protein required for catalytic activation and disassembly of the spliceosome. It contains two tandem helicase cassettes that both comprise dual RecA-like domains and a noncanonical Sec63 unit. The latter may bestow the enzyme with unique properties. We have determined crystal structures of ...

journal_title：Molecular cell

authors： Pena V,Jovin SM,Fabrizio P,Orlowski J,Bujnicki JM,Lührmann R,Wahl MC

更新日期：2009-08-28 00:00:00

abstract：:Defective ER-resident membrane proteins need to be ejected into the cytoplasm in order to be degraded by the proteasome, but the exact mechanism remains unclear. In this issue of Molecular Cell, Neal et al. (2018) reveal that the rhomboid pseudoprotease Dfm1 defines the central ERAD component for membrane protein disl...

journal_title：Molecular cell

authors： Avci D,Lemberg MK

更新日期：2018-01-18 00:00:00

abstract：:It has been known for some time that stimulation of heterotrimeric G protein-coupled receptors can cause cytoskeletal reorganization. A recent report in Developmental Cell demonstrates that the activation of a tyrosine kinase, C-terminal Src kinase, by heterotrimeric G protein subunits provides the trigger for Rho-dep...

journal_title：Molecular cell

authors： Luttrell LM

更新日期：2002-06-01 00:00:00

abstract：:mTOR senses nutrient and energy status to regulate cell survival and metabolism in response to environmental changes. Surprisingly, targeted mutation of Tsc1, a negative regulator of mTORC1, caused a broad reduction in miRNAs due to Drosha degradation. Conversely, targeted mutation of Raptor, an essential component of...

journal_title：Molecular cell

authors： Ye P,Liu Y,Chen C,Tang F,Wu Q,Wang X,Liu CG,Liu X,Liu R,Liu Y,Zheng P

更新日期：2015-02-19 00:00:00