Inhibition of both the extrinsic and intrinsic death pathways through nonhomotypic death-fold interactions.


:Death-fold domains constitute an evolutionarily conserved superfamily that mediates apoptotic signaling. These motifs, including CARD (caspase recruitment domain), DD (death domain), and DED (death effector domain), are believed to exert their effects solely through homotypic interactions. Herein we demonstrate that the CARD-containing protein ARC engages in nontraditional death-fold interactions to suppress both extrinsic and intrinsic death pathways. The extrinsic pathway is disrupted by heterotypic interactions between ARC's CARD and the DDs of Fas and FADD, which inhibit Fas-FADD binding and assembly of the death-inducing signaling complex (DISC). The intrinsic pathway is antagonized by ARC-Bax binding, involving ARC's CARD and the Bax C terminus. This inhibits Bax activation and translocation to the mitochondria. Knockdown of endogenous ARC facilitates DISC assembly and triggers spontaneous Bax activation and apoptosis. Conversely, physiological levels of ARC suppress these events. These studies establish a critical role for nonhomotypic death-fold interactions in the regulation of apoptosis.


Mol Cell


Molecular cell


Nam YJ,Mani K,Ashton AW,Peng CF,Krishnamurthy B,Hayakawa Y,Lee P,Korsmeyer SJ,Kitsis RN




Has Abstract


2004-09-24 00:00:00














  • Histone Acetyltransferase 1 Links Metabolism and Transcription to Cell-Cycle Progression.

    abstract::HAT1 is an essential gene in mammals that acetylates newly synthesized histone H4 and is involved in chromatin assembly and genome maintenance. In this issue of Molecular Cell, Gruber et al. (2019) show that HAT1 binds to and stimulates H4 gene expression in a growth-factor- and glucose-dependent manner. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Denu JM

    更新日期:2019-08-22 00:00:00

  • Spt6 Association with RNA Polymerase II Directs mRNA Turnover During Transcription.

    abstract::Spt6 is an essential histone chaperone that mediates nucleosome reassembly during gene transcription. Spt6 also associates with RNA polymerase II (RNAPII) via a tandem Src2 homology domain. However, the significance of Spt6-RNAPII interaction is not well understood. Here, we show that Spt6 recruitment to genes and the...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Dronamraju R,Hepperla AJ,Shibata Y,Adams AT,Magnuson T,Davis IJ,Strahl BD

    更新日期:2018-06-21 00:00:00

  • The MRN-CtIP pathway is required for metaphase chromosome alignment.

    abstract::Faithful duplication of the genome in S phase followed by its accurate segregation in mitosis is essential to maintain genomic integrity. Recent studies have suggested that proteins involved in DNA transactions are also required for whole-chromosome stability. Here we demonstrate that the MRN (Mre11, Rad50, and Nbs1) ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Rozier L,Guo Y,Peterson S,Sato M,Baer R,Gautier J,Mao Y

    更新日期:2013-03-28 00:00:00

  • MLKL Requires the Inositol Phosphate Code to Execute Necroptosis.

    abstract::Necroptosis is an important form of lytic cell death triggered by injury and infection, but whether mixed lineage kinase domain-like (MLKL) is sufficient to execute this pathway is unknown. In a genetic selection for human cell mutants defective for MLKL-dependent necroptosis, we identified mutations in IPMK and ITPK1...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Dovey CM,Diep J,Clarke BP,Hale AT,McNamara DE,Guo H,Brown NW Jr,Cao JY,Grace CR,Gough PJ,Bertin J,Dixon SJ,Fiedler D,Mocarski ES,Kaiser WJ,Moldoveanu T,York JD,Carette JE

    更新日期:2018-06-07 00:00:00

  • Fluorescence Amplification Method for Forward Genetic Discovery of Factors in Human mRNA Degradation.

    abstract::Nonsense-mediated decay (NMD) degrades mRNAs containing a premature termination codon (PTC). PTCs are a frequent cause of human genetic diseases, and the NMD pathway is known to modulate disease severity. Since partial NMD attenuation can potentially enhance nonsense suppression therapies, better definition of human-s...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Alexandrov A,Shu MD,Steitz JA

    更新日期:2017-01-05 00:00:00

  • An Atlas of Human Glycosylation Pathways Enables Display of the Human Glycome by Gene Engineered Cells.

    abstract::The structural diversity of glycans on cells-the glycome-is vast and complex to decipher. Glycan arrays display oligosaccharides and are used to report glycan hapten binding epitopes. Glycan arrays are limited resources and present saccharides without the context of other glycans and glycoconjugates. We used maps of g...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Narimatsu Y,Joshi HJ,Nason R,Van Coillie J,Karlsson R,Sun L,Ye Z,Chen YH,Schjoldager KT,Steentoft C,Furukawa S,Bensing BA,Sullam PM,Thompson AJ,Paulson JC,Büll C,Adema GJ,Mandel U,Hansen L,Bennett EP,Varki A,Vak

    更新日期:2019-07-25 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


    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

  • A Non-canonical Role of YAP/TEAD Is Required for Activation of Estrogen-Regulated Enhancers in Breast Cancer.

    abstract::YAP/TEAD are nuclear effectors of the Hippo pathway, regulating organ size and tumorigenesis largely through promoter-associated function. However, their function as enhancer regulators remains poorly understood. Through an in vivo proximity-dependent labeling (BioID) technique, we identified YAP1 and TEAD4 protein as...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Zhu C,Li L,Zhang Z,Bi M,Wang H,Su W,Hernandez K,Liu P,Chen J,Chen M,Huang TH,Chen L,Liu Z

    更新日期:2019-08-22 00:00:00

  • Insights into the influence of nucleotides on actin family proteins from seven structures of Arp2/3 complex.

    abstract::ATP is required for nucleation of actin filament branches by Arp2/3 complex, but the influence of ATP binding and hydrolysis are poorly understood. We determined crystal structures of bovine Arp2/3 complex cocrystallized with various bound adenine nucleotides and cations. Nucleotide binding favors closure of the nucle...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Nolen BJ,Pollard TD

    更新日期:2007-05-11 00:00:00

  • Scd6 targets eIF4G to repress translation: RGG motif proteins as a class of eIF4G-binding proteins.

    abstract::The formation of mRNPs controls the interaction of the translation and degradation machinery with individual mRNAs. The yeast Scd6 protein and its orthologs regulate translation and mRNA degradation in yeast, C. elegans, D. melanogaster, and humans by an unknown mechanism. We demonstrate that Scd6 represses translatio...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Rajyaguru P,She M,Parker R

    更新日期:2012-01-27 00:00:00

  • R-Loop Mediated trans Action of the APOLO Long Noncoding RNA.

    abstract::In eukaryotes, three-dimensional genome organization is critical for transcriptional regulation of gene expression. Long noncoding RNAs (lncRNAs) can modulate chromatin conformation of spatially related genomic locations within the nucleus. Here, we show that the lncRNA APOLO (AUXIN-REGULATED PROMOTER LOOP) recognizes...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Ariel F,Lucero L,Christ A,Mammarella MF,Jegu T,Veluchamy A,Mariappan K,Latrasse D,Blein T,Liu C,Benhamed M,Crespi M

    更新日期:2020-03-05 00:00:00

  • Magic Acts with the Cohesin Ring.

    abstract::Recent studies, including two in this issue of Molecular Cell (Elbatsh et al., 2016; Beckouët et al., 2016), cast light on how cohesin regulators harness the energy of ATP hydrolysis to open the cohesin ring and enable dynamic, regulated entrapment of chromosomes. ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Yu H

    更新日期:2016-02-18 00:00:00

  • Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking.

    abstract::Androgen receptor (AR) plays a critical role in the development and progression of prostate cancer, where it is a key therapeutic target. Here we report that, in contrast to estrogen receptor transcription complexes which form within minutes and recycle hourly, the levels of regulatory regions bound by AR complexes ri...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Wang Q,Carroll JS,Brown M

    更新日期:2005-09-02 00:00:00

  • Hos1 deacetylates Smc3 to close the cohesin acetylation cycle.

    abstract::Cohesion between sister chromatids is mediated by the chromosomal cohesin complex. In budding yeast, cohesin is loaded onto chromosomes during the G1 phase of the cell cycle. During S phase, the replication fork-associated acetyltransferase Eco1 acetylates the cohesin subunit Smc3 to promote the establishment of siste...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Borges V,Lehane C,Lopez-Serra L,Flynn H,Skehel M,Rolef Ben-Shahar T,Uhlmann F

    更新日期:2010-09-10 00:00:00

  • Building a Regulatory Network with Short Linear Sequence Motifs: Lessons from the Degrons of the Anaphase-Promoting Complex.

    abstract::The anaphase-promoting complex or cyclosome (APC/C) is a ubiquitin ligase that polyubiquitinates specific substrates at precise times in the cell cycle, thereby triggering the events of late mitosis in a strict order. The robust substrate specificity of the APC/C prevents the potentially deleterious degradation of non...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审


    authors: Davey NE,Morgan DO

    更新日期:2016-10-06 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


    authors: Campbell A

    更新日期:2002-05-01 00:00:00

  • Homologous recombination is promoted by translesion polymerase poleta.

    abstract::Two new studies provide in vivo ( [this issue of Molecular Cell]) and in vitro ( [this issue of Molecular Cell]) evidence that poleta functions to extend 3' strands exchanged during homologous recombination and raise the issue of how TLS polymerases are selected onto different substrates. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章,评审


    authors: Rattray AJ,Strathern JN

    更新日期:2005-12-09 00:00:00

  • BRCA1 recruitment to transcriptional pause sites is required for R-loop-driven DNA damage repair.

    abstract::The mechanisms contributing to transcription-associated genomic instability are both complex and incompletely understood. Although R-loops are normal transcriptional intermediates, they are also associated with genomic instability. Here, we show that BRCA1 is recruited to R-loops that form normally over a subset of tr...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Hatchi E,Skourti-Stathaki K,Ventz S,Pinello L,Yen A,Kamieniarz-Gdula K,Dimitrov S,Pathania S,McKinney KM,Eaton ML,Kellis M,Hill SJ,Parmigiani G,Proudfoot NJ,Livingston DM

    更新日期:2015-02-19 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

  • Yeast unravels epigenetic apoptosis control: deadly chat within a histone tail.

    abstract::An important paper by David Allis and colleagues (Ahn et al., 2006 [this issue of Molecular Cell]) describes a specific deacetylation/phosphorylation crosstalk at the histone H2B tail required for apoptosis induction in yeast, thus giving first insights into the poorly understood epigenetic regulation of cell death. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章,评审


    authors: Carmona-Gutierrez D,Madeo F

    更新日期:2006-10-20 00:00:00

  • RRM Transcription Factors Interact with NLRs and Regulate Broad-Spectrum Blast Resistance in Rice.

    abstract::Nucleotide-binding site leucine-rich repeat (NLR) receptors perceive pathogen effectors and trigger plant immunity. However, the mechanisms underlying NLR-triggered defense responses remain obscure. The recently discovered Pigm locus in rice encodes a cluster of NLRs, including PigmR, which confers broad-spectrum resi...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Zhai K,Deng Y,Liang D,Tang J,Liu J,Yan B,Yin X,Lin H,Chen F,Yang D,Xie Z,Liu JY,Li Q,Zhang L,He Z

    更新日期:2019-06-06 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

  • Too much of a good thing: the Prl-3 in p53's oyster.

    abstract::In this issue of Molecular Cell, Basak et al. (2008) identify Prl-3 as a p53-inducible gene acting in DNA damage-induced cell-cycle arrest. Both deletion and overexpression of Prl-3 can be cytostatic, adding to a growing list of genes whose expression must be carefully titrated for proper cell proliferation. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Hinds PW

    更新日期:2008-05-09 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

  • Multidomain Convergence of Argonaute during RISC Assembly Correlates with the Formation of Internal Water Clusters.

    abstract::Despite the relevance of Argonaute proteins in RNA silencing, little is known about the structural steps of small RNA loading to form RNA-induced silencing complexes (RISCs). We report the 1.9 Å crystal structure of human Argonaute4 with guide RNA. Comparison with the previously determined apo structure of Neurospora ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Park MS,Araya-Secchi R,Brackbill JA,Phan HD,Kehling AC,Abd El-Wahab EW,Dayeh DM,Sotomayor M,Nakanishi K

    更新日期:2019-08-22 00:00:00

  • PKR Senses Nuclear and Mitochondrial Signals by Interacting with Endogenous Double-Stranded RNAs.

    abstract::Protein kinase RNA-activated (PKR) induces immune response by sensing viral double-stranded RNAs (dsRNAs). However, growing evidence suggests that PKR can also be activated by endogenously expressed dsRNAs. Here, we capture these dsRNAs by formaldehyde-mediated crosslinking and immunoprecipitation sequencing and find ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Kim Y,Park J,Kim S,Kim M,Kang MG,Kwak C,Kang M,Kim B,Rhee HW,Kim VN

    更新日期:2018-09-20 00:00:00

  • Long noncoding RNAs add another layer to pre-mRNA splicing regulation.

    abstract::In this issue of Molecular Cell, Tripathi and coworkers (Tripathi et al., 2010) decode some of the functions of a long noncoding RNA MALAT1. They provide evidence that MALAT1 regulates alternative splicing by controlling the activity of the SR protein family of splicing factors. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Ankö ML,Neugebauer KM

    更新日期:2010-09-24 00:00:00

  • HATs off to PIC assembly.

    abstract::There are many regulated steps in the assembly of a transcription preinitiation complex (PIC). In this issue of Molecular Cell, Black et. al. (2006) reveal a catalytic switch mechanism in which autoacetylation of the HAT p300 triggers its dissociation from a promoter in a manner that is coupled to TFIID association. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章,评审


    authors: Pugh BF

    更新日期:2006-09-15 00:00:00

  • Autoinhibition of Bcr-Abl through its SH3 domain.

    abstract::Bcr-Abl is a dysregulated tyrosine kinase whose mechanism of activation is unclear. Here, we demonstrate that, like c-Abl, Bcr-Abl is negatively regulated through its SH3 domain. Kinase activity, transformation, and leukemogenesis by Bcr-Abl are greatly impaired by mutations of the Bcr coiled-coil domain that disrupt ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Smith KM,Yacobi R,Van Etten RA

    更新日期:2003-07-01 00:00:00

  • Interaction of translation initiation factor 3 with the 30S ribosomal subunit.

    abstract::Hydroxyl radical footprinting and directed probing from Fe(II)-derivatized IF3 have been used to map the interaction of IF3 relative to 16S rRNA and tRNA(Met)(f) in the 30S ribosomal subunit. Our results place the two domains of IF3 on opposite sides of the initiator tRNA, with the C domain at the platform interface a...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Dallas A,Noller HF

    更新日期:2001-10-01 00:00:00