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Showing papers in "Molecular Cell in 2006"


Journal ArticleDOI
TL;DR: It is shown that rapamycin inhibits the assembly of mTORC2 and that, in many cell types, prolongedRapamycin treatment reduces the levels of m TORC2 below those needed to maintain Akt/PKB signaling.

2,621 citations


Journal ArticleDOI
TL;DR: This study reveals previously unappreciated roles for lysine acetylation in the regulation of diverse cellular pathways outside of the nucleus, including many longevity regulators and metabolism enzymes.

1,422 citations


Journal ArticleDOI
TL;DR: Phylogenetic analyses of the components of the human elongation control machinery indicate that the number of mechanisms utilized to regulate P-TEFb function increased as organisms developed more complex developmental patterns.

1,071 citations


Journal ArticleDOI
TL;DR: The results reveal the biochemical mechanism underlying the essential signaling function of NEMO and provide direct evidence that signal-induced site-specific ubiquitination of RIP1 is required for IKK activation.

971 citations


Journal ArticleDOI
TL;DR: The results demonstrate that the control of MCL-1 stability by GSK-3 is an important mechanism for the regulation of apoptosis by growth factors, PI3K, and AKT.

851 citations


Journal ArticleDOI
TL;DR: Growing evidence challenges the conventional view that Mdm2 is essential for p53 turnover, and the discoveries of MdmX, HAUSP, ARF, COP1, Pirh2, and ARF-BP1 continue to uncover the multiple facets of this pathway.

836 citations


Journal ArticleDOI
TL;DR: Results suggest that repression by short RNAs, and thus probably miRNAs, is primarily due to ribosome drop off during elongation of translation.

823 citations


Journal ArticleDOI
TL;DR: PALB2 licenses key cellular biochemical properties of BRCA2 and ensures its tumor suppression function, as well as enabling homologous recombination (HR)-based, error-free DNA double-strand break repair (DSBR) and intra-S phase DNA damage checkpoint control.

797 citations


Journal ArticleDOI
TL;DR: A previously unknown posttranslational modification of the DNA-binding domain of p53 is described, acetylation of lysine 120 (K120), which occurs rapidly after DNA damage and is catalyzed by the MYST family acetyltransferases hMOF and TIP60.

713 citations


Journal ArticleDOI
TL;DR: It is demonstrated that Tip60-dependent acetylation of p53 at K120 modulates the decision between cell-cycle arrest and apoptosis, and it reveals that the DNA-binding core domain is an important target for p53 regulation by posttranslational modifications.

689 citations


Journal ArticleDOI
TL;DR: Overexpression of most toxic genes resulted in phenotypes different from known deletion mutant phenotypes, suggesting that overexpression phenotypes usually reflect a specific regulatory imbalance rather than disruption of protein complex stoichiometry.

Journal ArticleDOI
TL;DR: A somatic mutation and a gene variation in human lung cancer cells that change glycine to cysteine in the DGR domain are found, introducing local conformational changes that reduce Keap1's affinity for Nrf2.

Journal ArticleDOI
TL;DR: It is suggested that MDC1, as a signal amplifier of the ATM pathway, is vital in controlling proper DNA damage response and maintaining genomic stability.

Journal ArticleDOI
TL;DR: Direct observation of actin filaments by evanescent wave microscopy established a clear paradigm for actin turnover by cofilin in cells: low concentrations favor severing, whereas high concentrations favor nucleation.

Journal ArticleDOI
TL;DR: It is shown that increased variability in gene expression, affected by the sequence of the TATA box, can be beneficial after an acute change in environmental conditions.

Journal ArticleDOI
TL;DR: Since INGs, HBO1, and MOZ/MORF contribute to oncogenic transformation, the multisubunit assemblies characterized here underscore the critical role of epigenetic regulation in cancer development.

Journal ArticleDOI
TL;DR: It is reported here that hypoxia inhibits mRNA translation by suppressing multiple key regulators, including eIF2alpha, eEF2, and the mammalian target of rapamycin (mTOR) effectors 4EBP1, p70S6K, and rpS6, independent of HIF.

Journal ArticleDOI
TL;DR: These studies uncover diverse substrate receptors for Cul4 and identify Cdt2 as a conserved component of the Cul4-Ddb1 E3 that is essential to destroy Cdt1 and ensure proper cell cycle regulation of DNA replication.

Journal ArticleDOI
TL;DR: It is reported here that Per1 provides an important link between the circadian system and the cell cycle system and support the hypothesis that disruption of core clock genes may lead to cancer development.

Journal ArticleDOI
TL;DR: It is proposed that the coordinated action of checkpoint, recombination, and translesion synthesis-mediated processes at the fork and behind the fork preserves the integrity of replicating chromosomes by allowing efficient replication restart and filling the resulting ssDNA gaps.

Journal ArticleDOI
TL;DR: Quantitative mass spectrometry demonstrated that more than 50% of all EGFR bound ubiquitin was in the form of polyubiquitin chains, primarily linked through Lys63, which provides direct evidence for the role of EGFR ubiquitination in receptor targeting to the lysosome and implicate Lys63-linked polyubiquein chains in this sorting process.

Journal ArticleDOI
TL;DR: It is proposed that two-metal-ion catalysis greatly enhances substrate recognition and catalytic specificity in DNA and RNA polymerases.

Journal ArticleDOI
TL;DR: The studies uncover CUL4-DDB-ROC1 as a histone ubiquitin ligase and demonstrate that histone H3 and H4 ubiquitylation participates in the cellular response to DNA damage.

Journal ArticleDOI
TL;DR: It is suggested that phy-induced phosphorylation of proteins such as PIF3 may represent the primary intermolecular signaling transaction of the activated photoreceptor, tagging the target protein for proteosomal degradation, possibly in nuclear speckles.

Journal ArticleDOI
TL;DR: It is demonstrated that PML contains a SUMO binding motif that is independent of its SUMOylation sites and is surprisingly necessary for PML-NB formation, and it is proposed that the PML RING domain is critical forPML SUMoylation and PML -NB formation.

Journal ArticleDOI
TL;DR: It is shown that phosphorylation by protein kinase C of S181 within the polybasic region promotes rapid dissociation of K-Ras from the PM and association with intracellular membranes, including the outer membrane of mitochondria where phospho-K-RAS interacts with Bcl-XL.

Journal ArticleDOI
TL;DR: Recent papers suggest a more dynamic model, with rapid turnover of acetylation observed at nontranscribing "poised" genes and shown to be an important determinant of transcriptional efficiency upon gene induction.

Journal ArticleDOI
TL;DR: The mechanistic aspects of these important arms of the host innate response to dsRNA and a few viral strategies utilized to counteract them are discussed.

Journal ArticleDOI
TL;DR: It is shown that CSB and CSA display differential roles in recruitment of TCR-specific factors and that assembly for TCR occurs without disruption of the UV-stalled RNA polymerase II (RNAPIIo).

Journal ArticleDOI
TL;DR: It is demonstrated that arsenic trioxide-induced sumoylation of PML correlates with a change of endogenous Daxx partitioning from GR-regulated gene promoter to PODs and a relief of DAXx repression on GR target gene expression, which provides mechanistic insights into DaxX in SUMO-dependent transcriptional control and subnuclear compartmentalization.