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Showing papers in "Molecular Cell in 2005"


Journal ArticleDOI
TL;DR: The results suggest that apoptosis relies on selective interactions between particular subsets of these proteins and that it should be feasible to discover BH3-mimetic drugs that inactivate specific prosurvival targets.

1,793 citations


Journal ArticleDOI
TL;DR: Depletion of VISA inhibits virus-triggered and RIG-I-mediated activation of IRF-3, NF-kappaB, and the IFN-beta promoter, suggesting that VISA plays a central role in virus- Triggered TLR3-independent IFn-beta signaling.

1,692 citations


Journal ArticleDOI
TL;DR: The diverse effects of SUMO modification are discussed and models proposed to explain SUMO actions.

1,646 citations


Journal ArticleDOI
TL;DR: It is shown that proliferating mammalian cells have a cell-cycle checkpoint that responds to glucose availability and is regulated by AMP-activated protein kinase (AMPK), acell-cycle arrest that occurs despite continued amino acid availability and active mTOR.

1,541 citations


Journal ArticleDOI
TL;DR: A unified model of BH3 domain function is supported, encompassing both positive and negative regulation of other Bcl-2 family members, and the simple inhibition of antiapoptotic functions is insufficient to induce apoptosis unless a direct activator of Bax or Bak is present.

1,200 citations


Journal ArticleDOI
TL;DR: Proteomic analysis revealed that Brd4 interacts with cyclinT1 and Cdk9 that constitutes core positive transcription elongation factor b (P-TEFb) and is a positive regulatory component of P- TEFb, which alternately interacts with Brd 4 and the inhibitory subunit to maintain functional equilibrium in the cell.

1,120 citations


Journal ArticleDOI
TL;DR: Recent insights into the molecular processes regulated by arginine methylation in normal and diseased cells are described.

1,077 citations


Journal ArticleDOI
TL;DR: In this article, the deacetylase HDAC6 was shown to be a target of the molecular chaperone heat shock protein 90 (Hsp90) and its accessory cochaperones.

1,056 citations


Journal ArticleDOI
TL;DR: It is shown that in stress-induced cells, the 7SK/HEXIM1-bound P-TEFb is quantitatively converted into the Brd4-associated form, which is necessary to form the transcriptionally active P-teFb, recruits P- TEFb to a promoter, and enables P-TFb to contact the Mediator complex, a potential target for the Br d4-mediated recruitment.

1,016 citations


Journal ArticleDOI
TL;DR: The results suggest that EZH2-mediated H3-K27 methylation functions upstream of PRC1 and establishes a critical role for Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing.

871 citations


Journal ArticleDOI
TL;DR: PHLPP levels are markedly reduced in several colon cancer and glioblastoma cell lines that have elevated Akt phosphorylation, consistent with PHLPP terminating Akt signaling by directly dephosphorylating and inactivating Akt.

Journal ArticleDOI
TL;DR: It is shown that CoREST endows LSD1 with the ability to demethylate nucleosomal substrates and that it protects LSD1 from proteasomal degradation in vivo, suggesting that hypoacetylated nucleosomes may be the preferred physiological substrate.

Journal ArticleDOI
TL;DR: It is shown that H3K9 di- and trimethylation occur in the transcribed region of active genes in mammalian chromatin and this modification is dynamic, as it increases during activation of transcription and is rapidly removed upon gene repression.

Journal ArticleDOI
TL;DR: Six phosphorylation sites are identified that contribute to the downregulation of Raf-1 after mitogen stimulation and elucidate a critical Raf- 1 regulatory mechanism that contributes to the sensitive, temporal modulation of Ras signaling.

Journal ArticleDOI
TL;DR: Modulation of isoform production of cell death proteins via pharmaceutical manipulation of alternative splicing may open up new therapeutic avenues for the treatment of disease.

Journal ArticleDOI
TL;DR: It is proposed that USP1 deubiquitinates FANCD2 when cells exit S phase or recommence cycling after a DNA damage insult and may play a critical role in the FA pathway by recycling FAN CD2.

Journal ArticleDOI
TL;DR: The results link the pattern of preferential deacetylation at coding regions to the underlying patterns of H3-K36 methylation and phosphorylation of the RNA polymerase II C-terminal domain, and ultimately to the mechanism by which repressive chromatin structure is restored after transcriptional elongation.

Journal ArticleDOI
TL;DR: Using chromosome conformation capture (3C), it is shown that the hematopoietic transcription factor GATA-1 and its cofactor FOG-1 are required for the physical interaction between the beta-globin locus control region (LCR) and thebeta-major globin promoter.

Journal ArticleDOI
TL;DR: The combined genetic, cytological, and biochemical results suggest that SlmA is a DNA-associated division inhibitor that is directly involved in preventing Z ring assembly on portions of the membrane surrounding the nucleoid.

Journal ArticleDOI
TL;DR: A mechanism by which HBV-X protein (HBX) upregulates beta-catenin through a docking motif of GSK-3beta is reported, which is supported by immunohistochemical staining in different human tumors, including cancers of the liver, breast, kidney, and stomach.

Journal ArticleDOI
TL;DR: It is reported that in humans, the 600 kDa RNF20/40 complex is the E3 ligase and UbcH6 is the ubiquitin E2-conjugating enzyme for H2B-Lys120 monoubiquitination, and the hPAF complex is recruited to transcriptionally active genes in vivo.

Journal ArticleDOI
TL;DR: It is shown that Srs2p physically interacts with sumoylated PCNA, which contributes to the recruitment of the helicase to replication forks, suggesting a mechanism by which SUMO and ubiquitin cooperatively control the choice of pathway for the processing of DNA lesions during replication.

Journal ArticleDOI
TL;DR: It is reported that production of protein aggregates specifically targeted to either the nucleus or cytosol leads to global impairment of UPS function in both cellular compartments and is independent of sequestration of aggregates into cytoplasmic inclusion bodies (IBs).

Journal ArticleDOI
TL;DR: It is shown that protein phosphatase 2A (PP2A) is involved in removing gamma-H2AX foci from chromatin and the effect of PP2A on gamma- H2AX levels is independent of ATM, ATR, or DNA-PK activity.

Journal ArticleDOI
TL;DR: Observations suggest that multiple proteins involved in human decapping are important subunits of PBs and are activated on ARE-mRNAs by the protein TTP.

Journal ArticleDOI
TL;DR: It is demonstrated that a cellular peptidyl-prolyl cis-trans isomerase, cyclophilin B (CyPB), is critical for the efficient replication of the hepatitis C virus (HCV) genome.

Journal ArticleDOI
TL;DR: A flavin mononucleotide (FMN)-dependent riboswitch from the ribDEAHT operon of Bacillus subtilis uses a transcription termination mechanism wherein formation of an RNA-FMN complex causesformation of an intrinsic terminator stem.

Journal ArticleDOI
TL;DR: It is reported that, in contrast to estrogen receptor transcription complexes which form within minutes and recycle hourly, the levels of regulatory regions bound by AR complexes rise over a 16 hr period and then slowly decline.

Journal ArticleDOI
TL;DR: The generation of Arabidopsis extracts that reproduce many aspects of RNA silencing reactions in vitro are described and it is found that specific members of the Dicer and Argonaute families have distinct biochemical activities, which provides insight into their roles within RNAsilencing pathways in Arabidoptera.

Journal ArticleDOI
TL;DR: The characteristics of the altered specificity enzyme establish that Sir2 enzymes contain a single site that participates in catalysis and nicotinamide regulation and provides additional insights into the Sir2 catalytic mechanism.