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Showing papers in "Molecular Cell in 2007"


Journal ArticleDOI
TL;DR: Five general features of site context that boost site efficacy are uncovered: AU-rich nucleotide composition near the site, proximity to sites for coexpressed miRNAs (which leads to cooperative action), proximity to residues pairing to miRNA nucleotides 13-16, positioning within the 3'UTR at least 15 nt from the stop codon, and positioning away from the center of long UTRs.

3,818 citations


Journal ArticleDOI
TL;DR: It is demonstrated that microRNAs (miRNAs) are important components of the p53 transcriptional network and miR-34a-responsive genes are highly enriched for those that regulate cell-cycle progression, apoptosis, DNA repair, and angiogenesis.

2,008 citations


Journal ArticleDOI
TL;DR: This work has witnessed an explosion in understanding of DNA damage sensing, signaling, and the complex interplay between protein phosphorylation and the ubiquitin pathway employed by the DDR network to execute the response to DNA damage.

1,639 citations


Journal ArticleDOI
TL;DR: The molecular mechanisms by which hydrogen peroxide is sensed and the increasing evidence that antioxidant enzymes play multiple, key roles as sensors and regulators of signal transduction in response to hydrogen peroxy are discussed.

1,464 citations


Journal ArticleDOI
TL;DR: It is reported that, in addition to regulating the expression of hundreds of protein-coding genes, p53 also modulates the levels of microRNAs (miRNAs) by binding to a perfect p53 binding site located within the gene that gives rise to miR-34a.

1,333 citations


Journal ArticleDOI
TL;DR: Neuron-specific microRNA miR-124 promotes NS development, at least in part by regulating an intricate network of NS-specific alternative splicing patterns.

1,319 citations


Journal ArticleDOI
TL;DR: An emerging model of cytoplasmic mRNA function is suggested in which the rates of translation and degradation of mRNAs are influenced by a dynamic equilibrium between polysomes and the mRNPs seen in P bodies.

1,311 citations


Journal ArticleDOI
TL;DR: It is proposed that the relative strengths of the rheb- and PRAS40-mediated inputs to m TORC1 set overall pathway activity and that insulin activates mTORC1 through the coordinated regulation of both.

1,220 citations


Journal ArticleDOI
TL;DR: It is hypothesize how the unique properties of the polyvalent chromatin fiber and associated effectors may amplify small differences in methyl-lysine recognition, simultaneously allowing for a dynamic chromatin architecture.

1,093 citations


Journal ArticleDOI
TL;DR: An increase in the free cytosolic calcium ([Ca(2+)](c) serves as a potent inducer of macroautophagy and as a target for the antiautophagy action of ER-located Bcl-2.

1,060 citations


Journal ArticleDOI
TL;DR: Crosstalk between different types of posttranslational modification is an emerging theme in eukaryotic biology and particularly prominent are the multiple connections between phosphorylation and ubiquitination.

Journal ArticleDOI
TL;DR: The existence of well-conserved mammalian mirtrons indicates their relatively ancient incorporation into endogenous regulatory pathways, and it is hypothesized that different animals may have independently evolved the capacity for this hybrid small RNA pathway.

Journal ArticleDOI
TL;DR: In this article, the authors identify a biologically active HMTase inhibitor that allows for the transient modulation of H3K9me2 marks in mammalian chromatin and demonstrate that transient incubation of several cell lines with BIX-01294 lowers bulk H3 K 9me2 levels that are restored upon removal of the inhibitor.

Journal ArticleDOI
TL;DR: The results suggest that Sch9 functions analogously to the mammalian TORC1 substrate S6K1 rather than the mTORC2 substrate PKB/Akt, and the AGC kinase Sch9 is a substrate of yeastTORC1.

Journal ArticleDOI
TL;DR: This work develops a computational method that utilizes gene expression data to show that two classes of circuits-corresponding to positive and negative transcriptional coregulation of a miRNA and its targets-are prevalent in the human and mouse genomes.

Journal ArticleDOI
TL;DR: A core group of genes involved in constitutive maintenance of ER function in all cell types and tissue- and condition-specific targets are identified and a cadre of unexpected targets that link XBP1 to neurodegenerative and myodegenerative diseases, as well as to DNA damage and repair pathways are identified.

Journal ArticleDOI
TL;DR: This review focuses on the various cellular functions of mammalian Argonaute proteins in conjunction with the different small RNA species that are known today.

Journal ArticleDOI
TL;DR: The chemical mechanisms for the known and potentially new classes of demethylases, the roles of these dem methylases in chromatin and transcription, and their potential biological functions and connections to human diseases are discussed.

Journal ArticleDOI
TL;DR: The findings provide the biochemical basis for understanding how inflammasome assembly and function are regulated, and shed light on NALP1 as a direct sensor of bacterial components in host defense against pathogens.

Journal ArticleDOI
TL;DR: The majority of AR binding regions contain noncanonical AR-responsive elements (AREs) and are identified as a cis-regulatory target of AR action in TMPRSS2, a gene fused to ETS transcription factors in the majority of prostate cancers.

Journal ArticleDOI
TL;DR: It is suggested that, in addition to its role in microtubule-dependent cell motility, HDAC6 influences actin-dependentCell motility by altering the acetylation status of cortactin, which, in turn, changes the F-actin binding activity of Cortactin.

Journal ArticleDOI
TL;DR: It is shown that SIRT1 is a positive regulator of liver X receptor (LXR) proteins, nuclear receptors that function as cholesterol sensors and regulate whole-body cholesterol and lipid homeostasis, and suggests that deacetylation of LXRs by Sirt1 may be a mechanism that affects atherosclerosis and other aging-associated diseases.

Journal ArticleDOI
TL;DR: It is suggested that methylated H3K4 serves to facilitate the competency of pre-mRNA maturation through the bridging of spliceosomal components to H3k4me3 via CHD1.

Journal ArticleDOI
TL;DR: The data unveil a mechanism to selectively terminate Akt-signaling pathways through the differential inactivation of specific Akt isoforms by specific PHLPP isoforms.

Journal ArticleDOI
TL;DR: Mutational analysis and studies of naturally occurring oxysterol ligands indicate that the transactivation and SUMOylation-dependent transrepression activities of LXRs can be independently regulated.

Journal ArticleDOI
TL;DR: This review focuses on the molecular and functional aspects of fHC that distinguish it from constitutive heterochromatin (cHC) and euchROMatin (EC) and discusses various concepts regarding the regulation of f HC structure.

Journal ArticleDOI
TL;DR: The findings demonstrate that HuR regulates SIRT1 expression, underscore functional links between the two stress-response proteins, and implicate Chk2 in these processes.

Journal ArticleDOI
TL;DR: The C termini of the proteasomal ATPases function like a "key in a lock" to induce gate opening and allow substrate entry in the 20S.

Journal ArticleDOI
TL;DR: It is shown that TNF also activates the Nox1 NADPH oxidase in mouse fibroblasts when cells undergo necrosis, suggesting that activation of Nox 1 through forming a complex with TNF signaling components plays a key role in TNF-induced necrotic cell death.

Journal ArticleDOI
TL;DR: PLU-1, a transcriptional repressor implicated in breast cancer, is identified as a histone demethylase enzyme that has the ability to reverse the trimethyl H3K4 modification state and is revealed to play an important role in the proliferation capacity of breast cancer cells through repression of tumor suppressor genes, including BRCA1.