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Showing papers in "Molecular Cell in 2008"


Journal ArticleDOI
TL;DR: AMPK directly phosphorylates the mTOR binding partner raptor on two well-conserved serine residues, and this phosphorylation induces 14-3-3 binding to raptor, uncovering a conserved effector of AMPK that mediates its role as a metabolic checkpoint coordinating cell growth with energy status.

3,328 citations


Journal ArticleDOI
TL;DR: HIF plays a central role in the transcriptional response to changes in oxygen availability and is modulated by FIH1-mediated asparagine hydroxylation, and HIF-modulatory drugs are now being developed for diverse diseases.

2,623 citations


Journal ArticleDOI
TL;DR: The results show that miR-10a may positively control global protein synthesis via the stimulation of ribosomal protein mRNA translation and ribosome biogenesis and hereby affect the ability of cells to undergo transformation.

1,352 citations


Journal ArticleDOI
TL;DR: It is demonstrated that JNK1-mediated multisite phosphorylation of Bcl-2 stimulates starvation-induced autophagy by disrupting the B cl-2/Beclin 1 complex, which defines a mechanism that cells use to regulate autophagic activity in response to nutrient status.

1,225 citations


Journal ArticleDOI
TL;DR: A mechanism whereby Kcnq1ot1 establishes lineage-specific transcriptional silencing patterns through recruitment of chromatin remodeling complexes and maintenance of these patterns through subsequent cell divisions occurs via targeting the associated regions to the perinucleolar compartment is described.

1,164 citations


Journal ArticleDOI
TL;DR: The construction of the piRNA system in the restricted developmental window in which methylation patterns are set during mammalian embryogenesis is examined, finding robust expression of two Piwi family proteins, MIWI2 and MILI.

1,080 citations


Journal ArticleDOI
TL;DR: It is demonstrated that AEG40730, a compound modeled on BIR-binding tetrapeptides, binds to cI AP1 and cIAP2, facilitates their autoubiquitination and proteosomal degradation, and causes a dramatic reduction in RIP1 ubiquitination.

1,000 citations


Journal ArticleDOI
TL;DR: EZH1 partially complements Ezh2 in executing pluripotency during ESC differentiation, suggesting that cell-fate transitions require epigenetic specificity.

958 citations


Journal ArticleDOI
Inha Heo1, Chirlmin Joo1, Jun Cho1, Minju Ha1, Jinju Han1, V. Narry Kim1 
TL;DR: The Lin28-mediated downregulation of let-7 may play a key role in development, stem cell programming, and tumorigenesis and is provided for the posttranscriptional regulation of miRNA biogenesis by Lin28 which is highly expressed in undifferentiated cells and certain cancer cells.

946 citations


Journal ArticleDOI
TL;DR: This review focuses on recent findings pertinent to acetylation of nonhistone proteins and emphasizes how this modification might crosstalk with phosphorylation, methylation, ubiquitination, sumoylation, and others to form code-like multisite modification programs for dynamic control of cellular signaling under diverse conditions.

943 citations


Journal ArticleDOI
TL;DR: A model how de novo DNA methylation and dynamic switches in Polycomb targets restrict pluripotency and define the developmental potential of progenitor cells is suggested.

Journal ArticleDOI
TL;DR: It is shown that < or =25% of DSBs require ATM signaling for repair, and this percentage correlates with increased chromatin but not damage complexity, which suggests that the importance of ATM signalling for DSB repair increases as the heterochromatic component of a genome expands.

Journal ArticleDOI
TL;DR: It is reported that the mammalian homologs Ezh1 and Ezh2 form similar PRC2 complexes but exhibit contrasting repressive roles, and Ez h1 knockdown was ineffectual on global H3K27me2/3 levels, while Ezh 1 directly and robustly represses transcription from chromatinized templates and compacts chromatin in the absence of the methyltransferase cofactor SAM.

Journal ArticleDOI
TL;DR: A class of small RNAs in human cells that originate from snoRNAs and can function like miRNAs is identified, suggesting a role for ACA45-processing products in posttranscriptional gene silencing.

Journal ArticleDOI
TL;DR: OP (Oligomerized Pool ENgineering), a rapid, publicly available strategy for constructing multifinger arrays, which is more effective than the previously published modular assembly method and provides an "open-source" method for rapidly engineering highly active zinc-finger arrays.

Journal ArticleDOI
TL;DR: It is demonstrated the existence of a functional respirasome and a structural organization model is proposed that accommodates these findings.

Journal ArticleDOI
TL;DR: New evidence is discussed that links histone ubiquitination to other chromatin modifications, which has provided a model for the role of H2B ubiquitinations, in particular, in transcription initiation and elongation.

Journal ArticleDOI
TL;DR: This work combines kinase-selective affinity purification with quantitative mass spectrometry to analyze the cell-cycle regulation of protein kinases and reveals numerous unknown M phase-induced phosphorylation sites on kinases with established mitotic functions.

Journal ArticleDOI
TL;DR: These findings demonstrate that 21U-RNAs are the piRNAs of C. elegans and link this class of small RNAs and their associated Piwi Argonaute to the maintenance of temperature-dependent fertility.

Journal ArticleDOI
TL;DR: The anchor-away technique depletes the nucleus of Saccharomyces cerevisiae of a protein of interest by conditional tethering to an abundant cytoplasmic protein (the anchor) by appropriate gene tagging and rapamycin-dependent heterodimerization.

Journal ArticleDOI
TL;DR: It is reported here that TRAF6 is specifically required for the Smad-independent activation of JNK and p38, and its carboxyl TRAF homology domain physically interacts with TGF-beta receptors.

Journal ArticleDOI
TL;DR: It is shown that the C-terminal regulatory domain RD of RIG-I binds viral RNA in a 5'-triphosphate-dependent manner and activates the RIG -I ATPase by RNA-dependent dimerization.

Journal ArticleDOI
TL;DR: It is demonstrated that the Staphylococcus aureus agr quorum-sensing regulon is divided into control of metabolism and PSM cytolysin genes, which occurs independently of the small regulatory RNA RNAIII, and RNAIII-dependent control of additional virulence genes.

Journal ArticleDOI
TL;DR: It is suggested that the bipartite structure of CTD regulates RIG-I on encountering viral RNA patterns and CTD coincides with the autorepression domain.


Journal ArticleDOI
TL;DR: The complete ectodomain of integrin alpha(IIb)beta(3) reveals a bent, closed, low-affinity conformation, the beta knee, and a mechanism for linking cytoskeleton attachment to high affinity for ligand.

Journal ArticleDOI
TL;DR: The current understanding of the roles of IAPs in apoptotic and nonapoptotic processes is reviewed and the notion that the latter represents the primary physiologic activities of I APs is explored.

Journal ArticleDOI
TL;DR: It is found that strand-specific mutation rates strongly depend on the orientation of a reporter gene relative to an adjacent replication origin, in a manner implying that >90% of Pol delta replication is performed using the lagging strand template.

Journal ArticleDOI
TL;DR: It is shown that human Alu RNA, transcribed from short interspersed elements (SINEs), is a transacting transcriptional repressor during the cellular heat shock response.

Journal ArticleDOI
TL;DR: The downregulation of gene expression by miRNAs and siRNAs is a complex process involving both translational repression and accelerated mRNA turnover, each of which appears to occur by multiple mechanisms.