Showing papers in "Molecular Cell in 2000"

TL;DR: Protein kinases that phosphorylate the alpha subunit of eukaryotic initiation factor 2 (eIF2alpha) are activated in stressed cells and negatively regulate protein synthesis, resulting in the induction of the downstream gene CHOP (GADD153).

TL;DR: The identification of a new locus, FLS2, is described, which is ubiquitously expressed and encodes a putative receptor kinase and shares structural and functional homologies with known plant resistance genes and with components involved in the innate immune system of mammals and insects.

TL;DR: In this paper, the authors report that mutating the gene encoding the ER stress-activated eIF2alpha kinase PERK abolishes the phosphorylation of eIF 2 alpha in response to accumulation of malfolded proteins in the ER resulting in abnormally elevated protein synthesis and higher levels of ER stress.

TL;DR: A potent, nonsteroidal FXR ligand is used to show that FXR induces expression of small heterodimer partner 1 (SHP-1), an atypical member of the nuclear receptor family that lacks a DNA-binding domain that provides a molecular basis for the coordinate suppression of CYP7A1 and other genes involved in bile acid biosynthesis.

TL;DR: It is shown that S1P and S2P are required for the ER stress response as well as for lipid synthesis, and ATF6 processing did not require SCAP, which is essential for SREBP processing.

TL;DR: Bax and Bak have overlapping roles in the regulation of apoptosis during mammalian development and tissue homeostasis and are found to be developmentally normal and reproductively fit.

TL;DR: The isolation and characterization of a novel cDNA (Ireg1) encoding a duodenal protein that is localized to the basolateral membrane of polarized epithelial cells are described and it is concluded that IREG1 represents the long-sought duodental iron export protein and is upregulated in the iron overload disease, hereditary hemochromatosis.

TL;DR: An elaborate autoregulatory cascade mediated by nuclear receptors for the maintenance of hepatic cholesterol catabolism is revealed, showing that repression is coordinately regulated by a triumvirate of nuclear receptors, including the bile acid receptor, FXR, and the promoter-specific repressor, SHP.

TL;DR: The determinant of verapamil-reversible chloroquine resistance (CQR) in a Plasmodium falciparum genetic cross maps to a 36 kb segment of chromosome 7 that harbors a 13-exon gene, pfcrt, having point mutations that associate completely with CQR in parasite lines from Asia, Africa, and South America.

TL;DR: Smad7 is defined as an adaptor in an E3 ubiquitin-ligase complex that targets the TGF beta receptor for degradation, and mutants that interfere with recruitment of Smurf2 to the receptors are compromised in their inhibitory activity.

TL;DR: In this paper, the Cre-loxP system was used to inactivate the insulin receptor gene in hepatocytes, and the effect of the loss of direct insulin action in liver was investigated.

TL;DR: This model provides a structural basis for FGFR activation by small molecule Heparin analogs and may facilitate the design of heparin mimetics capable of modulating FGF signaling.

TL;DR: It is shown that an additional processing event occurs in the extracellular part of the receptor, preceding cleavage by the gamma-secretase-like activity, and experiments carried out on TACE-/- bone marrow-derived monocytic precursor cells suggest that this metalloprotease plays a prominent role in the activation of the Notch pathway.

TL;DR: Interestingly, LY294002 and the lead compound on which it was designed, quercetin, as well as the closely related flavonoid myricetin bind PI3K in remarkably different orientations that are related to each other by 180 degrees rotations.

TL;DR: The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors for fatty acids (FAs) that regulate glucose and lipid homeostasis as mentioned in this paper.

TL;DR: The human paracaspase prodomain binds Bcl10, a protein involved in the t(1;14)(p22;q32) translocation of mucosa-associated lymphoid tissue (MALT) lymphoma, and it is found that this fusion activates NF-kappaB and that the caspase domain is required for this function, since mutation of the conserved catalytic cysteine attenuates NF- kappaB activation.

TL;DR: It is demonstrated that ligand binding facilitates cleavage at a novel site (S2), within the extracellular juxtamembrane region, which serves to release ectodomain repression of NICD production.

TL;DR: In this paper, the authors show that chronic hyperinsulinemia downregulates the mRNA for IRS-2, an essential component of the insulin-signaling pathway in liver, thereby producing insulin resistance.

TL;DR: Evidence is provided that biochemically similar chromatin-remodeling complexes have dramatically different functions during mammalian development.

TL;DR: It is suggested that late larval activation of let-7 RNA expression downregulates LIN-41 to relieve inhibition of lin-29, and this work concludes that the C. elegans heterochronic gene lin-41 negatively regulates the timing of LIN-29 adult specification transcription factor expression.

TL;DR: It is reported that histone acetylation and phosphorylation are synergistic, and this results illustrate how the addition of multiple histone modifications may be coupled during the process of gene expression.

TL;DR: The 1.8 A resolution crystal structure of the complex between a VDR ligand-binding domain (LBD) construct lacking the highly variable VDR-specific insertion domain and vitamin D shows that the N-terminal part of the LBD is essential for its structural and functional integrity while the large insertion peptide is dispensable.

TL;DR: It is shown that Scc2p forms a complex with a novel protein, Scc4p, which is also necessary for sister cohesion, suggesting that a major role for the SCC2p/SCC4p complex is to facilitate the loading of cohesin complexes onto chromosomes.

TL;DR: The Spo11 protein initiates meiotic recombination by generating DNA double-strand breaks (DSBs) and is required for meiotic synapsis in S. cerevisiae, but it is speculated that there is an additional role for Spo11, after it generates DSBs, insynapsis.

TL;DR: Genetic analysis guided by the structure reveals a regulatory element N-terminal to the proteolytic domain that is required for cell growth in yeast and elucidates determinants of SUMO recognition, processing, and deconjugation.

TL;DR: The results support the view that mammalian checkpoint responses to meiotic recombination and/or synapsis defects are sexually dimorphic and propose that recombination initiation precedes and is required for normalsynapsis in mammals.

TL;DR: It is shown that RNAi requires duplex formation between the two trigger strands, that the duplex must include a region of identity between trigger and target RNAs, and that duplexes as short as 26 bp can trigger RNAi.

TL;DR: A null mutation in the SCP3 gene was generated, and it was noted that homozygous mutant males were sterile due to massive apoptotic cell death during meiotic prophase, and a residual chromatin organization remained in the mutant meiotic cells.

TL;DR: In this paper, survival factors trigger the phosphorylation of the pro-apoptotic Bcl-2 family member BAD at a site (Ser-155) within the BAD BH3 domain.