Showing papers in "Molecular Cell in 2003"
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TL;DR: A signaling pathway initiated by eIF2alpha phosphorylation protects cells against metabolic consequences of ER oxidation by promoting the linked processes of amino acid sufficiency and resistance to oxidative stress.
2,920 citations
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TL;DR: Evidence that p53 translocation to the mitochondria occurs in vivo in irradiated thymocytes is provided and it is shown that the p53 protein can directly induce permeabilization of the outer mitochondrial membrane by forming complexes with the protective BclXL and Bcl2 proteins, resulting in cytochrome c release.
1,751 citations
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TL;DR: A human ortholog of Sir2p, sirtuin type 2 (SIRT2), is a predominantly cytoplasmic protein that colocalizes with microtubules and is established as a bona fide tubulin deacetylase.
1,434 citations
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TL;DR: Hypermethylated H3-K4 within the mRNA coding region persists for considerable time after transcriptional inactivation and Set1 dissociation from the chromatin, indicating that H3/K4 hypermethylation provides a molecular memory of recent transcriptional activity.
1,140 citations
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TL;DR: The data underscore the selective presence of distinct histone lysine methylation states in partitioning chromosomal subdomains but also reveal a surprising plasticity in propagating methylation patterns in eukaryotic chromatin.
1,129 citations
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TL;DR: The number of new proteins emerging with no prior connection to splicing was surprising and it would be premature to label these proteins as bona fide splicing factors, yet many were identified multiple times in complexes purified under diverse conditions or from different organisms.
1,020 citations
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TL;DR: Evidence is provided that TSC1/2 is a GAP for the small GTPase Rheb and that insulin-mediated RheB activation is PI3K dependent and that Rhe b overexpression induces S6K1 phosphorylation and inhibits PKBosphorylation, as do loss-of-function mutations in TSC 1/2.
1,004 citations
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TL;DR: A unified caspase activation hypothesis is proposed whereby apical caspases are activated by dimerization of monomeric zymogens, and single amino acid substitutions at the dimer interface abrogate the activity of caspased-8 and -9 introduced into recipient mammalian cells.
1,003 citations
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TL;DR: It is proposed that the opposing effects on mTOR activity of the GbetaL- and raptor-mediated interactions regulate the mTOR pathway.
950 citations
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TL;DR: A mechanistic view of ErbB receptor homo- and heterodimerization is outlined, which suggests new approaches for interfering with these processes when they are implicated in human cancers.
927 citations
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TL;DR: YAP overexpression increases, while YAP depletion decreases, p73-mediated apoptosis following DNA damage, in an Akt inhibitable manner, and Akt phosphorylation of YAP may thus suppress the induction of the proapoptotic gene expression response following cellular damage.
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TL;DR: The structure reveals an autoinhibited configuration, where the dimerization interface recently identified in activated sEGFR structures is completely occluded by intramolecular interactions, which contrasts starkly with other RTK activation mechanisms and suggests new approaches for designing ErbB receptor antagonists.
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TL;DR: Different methylated states of H3 Lys9 are directed by specific histone methyltransferases to "mark" distinct domains of silent chromatin.
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TL;DR: It is reported that the Paf1 protein complex, which is associated with the elongating RNA polymerase II, is required for methylation of lysines 4 and 79 of histone H3 and for silencing of expression of a telomere-associated gene.
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TL;DR: It is demonstrated that proteasome-mediated degradation and hER alpha-mediated transactivation are inherently linked and act to continuously turn over hERalpha on responsive promoters.
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TL;DR: It is shown how the bimodal translational and posttranslational inhibitory effects of Vif on APOBEC3G combine to markedly suppress the expression of this potent antiviral enzyme in virally infected cells, thereby effectively curtailing the incorporation of APOBec3G into newly formed HIV-1 virions.
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TL;DR: It is demonstrated that monomeric caspase-9 is catalytically inactive due to the absence of a supporting sequence element that could be provided by homodimerization, which defines a unified mechanism for the activation of all caspases.
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TL;DR: It is shown that expression of a human equivalent to Drosophila's C4 pol II in human cultured cells affects alternative splicing of the fibronectin EDI exon and adenovirus E1a pre-mRNA and resplices of the Hox gene Ultrabithorax are stimulated, which demonstrates the transcriptional control ofAlternative splicing on an endogenous gene.
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TL;DR: It is shown, using hpr1Delta mutants, that the nascent mRNA can diminish transcription elongation efficiency and promote recombination and support a model to explain the connection between recombination, transcription, and mRNA metabolism.
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TL;DR: It is reported that ALK5 is important for TGFbeta/ALK1 signaling; endothelial cells lacking AlK5 are deficient in TGF beta/ALK 1-induced responses and that theALK5 kinase activity is required for optimal ALK1 activation.
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TL;DR: It is demonstrated that NF-kappaB function is regulated by Pin1-mediated prolyl isomerization and ubiquitin-mediated proteolysis of its p65/RelA subunit, enabling new insight into the pathogenesis and treatment of some human diseases such as cancers.
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TL;DR: It is shown that recruitment of Htz1 to chromatin requires the SWR-C, a TFIID-interacting protein that recognizes acetylated histone tails that promotes gene expression near silent heterochromatin.
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TL;DR: The crystal structure of residues 1-509 of ErbB2 reveals an activated conformation similar to that of the EGFR when complexed with ligand and very different from that seen in the unactivated forms ofErbB3 or EGFR.
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TL;DR: These results represent a description of general rules governing substrate recognition by a AAA+ family ATPase and suggest strategies for regulation of protein degradation.
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TL;DR: Results indicate that Sir2 regulates muscle gene expression and differentiation by possibly functioning as a redox sensor in response to exercise, food intake, and starvation, Sir2 may sense modifications of the redox state and promptly modulate gene expression.
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TL;DR: The recognition between Aurora-A and TPX2 resembles that between the cAPK catalytic core and its flanking regions, suggesting this molecular mechanism may be a recurring theme in kinase regulation.
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TL;DR: A conserved family of coactivators, designated TORCs, for Transducers of Regulated CREB activity, that enhances CRE-dependent transcription via a phosphorylation-independent interaction with the bZIP DNA binding/dimerization domain of CREB is characterized.
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TL;DR: Genome-wide transcriptional profiling of human epithelial cells revealed that repression of Id inhibitors of differentiation (Id1, Id2, and Id3) is a general feature of the TGFbeta cytostatic program.
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TL;DR: It is demonstrated that MazF toxin encoded by "mazEF addiction module" is a sequence-specific (ACA) endoribonuclease functional only for single-stranded RNA, and is, therefore, functionally distinct from RelE, another E. coli toxin, which assists mRNA cleavage at the A site on ribosomes.
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TL;DR: In this paper, the authors showed that the lysine-destruction motif spacing is a determinant of ubiquitination efficiency and also provided a mechanistic basis for substrate selection.