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Showing papers in "Molecular Cell in 1999"


Journal ArticleDOI
TL;DR: It is demonstrated here that mice chimeric for wild-type and PPARγ null cells show little or no contribution of null cells to adipose tissue, whereas most other organs examined do not require PParγ for proper development.

1,871 citations


Journal ArticleDOI
TL;DR: Findings both confirm and expand the current known spectrum of physiological functions regulated by PPAR gamma, implicating a previously unrecognized dependence of the developing heart on a functional placenta.

1,813 citations


Journal ArticleDOI
TL;DR: It is suggested that FXR (BAR) is the endogenous biliary component that selectively activates the orphan nuclear receptor, FXR, and thus an important regulator of cholesterol homeostasis.

1,445 citations



Journal ArticleDOI
TL;DR: A caretaker role for BRCA1 is demonstrated in preserving genomic integrity by promoting homologous recombination and limiting mutagenic nonhomologous repair processes.

1,208 citations


Journal ArticleDOI
TL;DR: The regulation of the proapoptotic activity of the BH3-only protein Bim was examined and it was found that certain apoptotic stimuli disrupted the interaction between LC8 and the dynein motor complex and therefore constitutes an initiating event in apoptosis signaling.

1,103 citations


Journal ArticleDOI
TL;DR: This study identifies Cbl proteins as components of the ubiquitin ligation machinery and implies that they similarly suppress many other signaling pathways.

1,014 citations


PatentDOI
TL;DR: It is found that two human Smad proteins could specifically recognize an identical 8 bp palindromic sequences (GTCTAGAC) and this property is defined as a novel biochemical property of Smad protein that is likely to play a direct role in the biologic responses to TGF beta and related ligands.

1,009 citations


Journal ArticleDOI
TL;DR: Results define multiple roles for C/EBPα in adipogenesis and show that cross-regulation between PPARγ and C/ EBPα is a key component of the transcriptional control of this cell lineage.

939 citations


Journal ArticleDOI
TL;DR: It is concluded that even though tumorigenesis is a multistep process, remediation of a single genetic lesion may be sufficient to reverse malignancy.

867 citations


Journal ArticleDOI
TL;DR: Four additional c-Src structures in which this segment adopts an ordered but inhibitory conformation are reported, in which the ordered activation loop forms an alpha helix that stabilizes the inactive conformation of the kinase domain, blocks the peptide substrate-binding site, and prevents Tyr-416 phosphorylation.

Journal ArticleDOI
TL;DR: It is shown that mouse embryonic fibroblast cells carrying a targeted deletion of exon 11 of the Brca1 gene maintain an intact G1-S cell cycle checkpoint and proliferate poorly, however, a defective G2-M checkpoint in these cells is accompanied by extensive chromosomal abnormalities.

Journal ArticleDOI
TL;DR: Although mice lacking individual Src family kinases (SFKs) showed normal angiogenesis, mice deficient in pp60c-src or pp62c-yes showed no VEGF-induced vascular permeability (VP), yet fyn-/- mice displayed normal VP.

Journal ArticleDOI
TL;DR: Data indicate that ephrin-B2-EphB4 interactions are intrinsically required in vascular endothelial cells and are consistent with the idea that they mediate bidirectional signaling essential for angiogenesis.

Journal ArticleDOI
TL;DR: The results suggest that AP-3 functions in protein sorting to lysosomes and provide an example of a human disease in which altered trafficking of integral membrane proteins is due to mutations in a component of the sorting machinery.

Journal ArticleDOI
TL;DR: The anchoring of PKA to mitochondria represents a focused subcellular kinase/substrate interaction that inactivates BAD at its target organelle in response to a survival factor.

Journal ArticleDOI
TL;DR: The crystal structure of the T = 4 capsid has been solved at 3.3 A resolution, revealing a largely helical protein fold that is unusual for icosahedral viruses.

Journal ArticleDOI
TL;DR: It is shown that mitochondria are disrupted by mutations in a C. elegans dynamin-related protein (DRP-1) that contributes to the final stages of mitochondrial division by controlling scission of the mitochondrial outer membrane.

Journal ArticleDOI
TL;DR: Unexpectedly, both BRG1 and hBRM, the ATPase subunits of human SWI/SNF complexes, are capable of remodeling mono-nucleosomes and nucleosomal arrays as purified proteins.

Journal ArticleDOI
TL;DR: It is demonstrated that TRANCE activates the antiapoptotic serine/threonine kinase Akt/PKB through a signaling complex involving c-Src and TRAF6 and evidence of cross-talk between TRAF proteins and Src family kinases is provided.

Journal ArticleDOI
TL;DR: These structures reveal an evolutionarily conserved network of peptide-protein interactions within all 14-3-3 isotypes, explain both binding motifs, and identify a novel intrachain phosphorylation-mediated loop structure in one of the peptides.

Journal ArticleDOI
TL;DR: Using deletion mutants, it is shown that Relish is specifically required for the induction of the humoral immune response, including both antibacterial and antifungal peptides, and plays a key role in this response.

Journal ArticleDOI
TL;DR: Efficient exchange of ADP for ATP is promoted by Bcl-xL expression permitting oxidative phosphorylation to be regulated by cellular ATP/ADP levels and allowing mitochondria to adapt to changes in metabolic demand.

Journal ArticleDOI
TL;DR: It is demonstrated here that phosphorylation of AF-1 by MAP kinase (MAPK) leads to the recruitment of steroid receptor coactivator-1 (SRC-1) by ER beta in vitro and provides a molecular basis for ligand-independent activation by ERbeta via the MAPK pathway.

Journal ArticleDOI
TL;DR: High-resolution X-ray crystallography and complementary biophysical methods have revealed that this eIF4E recognition motif undergoes a disorder-to-order transition, adopting an L-shaped, extended chain/alpha-helical conformation when it interacts with a phylogenetically invariant portion of the convex surface of eif4E.

Journal ArticleDOI
TL;DR: Phenotypes of yeast elp1 delta cells demonstrated an involvement of elongator in transcriptional elongation as well as activation in vivo, and data indicate that the transition from transcriptional initiation to elongation involves an exchange of the multiprotein mediator complex for elongators in a reaction coupled to CTD hyperphosphorylation.

Journal ArticleDOI
TL;DR: Data indicate that colon cancer in humans is associated with loss-of-function mutations in PPAR gamma, the gamma isoform of the peroxisome proliferator-activated receptor that regulates adipocyte differentiation and has recently been shown to be expressed in neoplasia of the colon and other tissues.

Journal ArticleDOI
TL;DR: Elp3, the 60-kilodalton subunit of elongator/RNAPII holoenzyme, is identified as a highly conserved histone acetyltransferase (HAT) capable of acetylating core histones in vitro, suggesting a role for a novel, tightly RNAPII-associated HAT in transcription of DNA packaged in chromatin.

Journal ArticleDOI
TL;DR: Two highly conserved RING finger proteins, ROC1 and ROC2, that are homologous to APC11, a subunit of the anaphase-promoting complex, potentially constitute a wide variety of ubiquitin ligases.

Journal ArticleDOI
TL;DR: The crystal structure of the complex between Apo2L and the ectodomain of DR5 suggests general principles of binding and specificity for ligand recognition in the TNF receptor superfamily.