Showing papers in "Trends in Biochemical Sciences in 2005"

TL;DR: Because deregulation of NF-κB and IκB phosphorylations is a hallmark of chronic inflammatory diseases and cancer, newly designed drugs targeting these constitutively activated signalling pathways represent promising therapeutic tools.

TL;DR: The role of cyclin-dependent kinases (Cdks) in regulating the mammalian cell cycle and their potential use as therapeutic targets in cancer has been investigated in this paper.

TL;DR: The existence of multifaceted roles of glycolytic proteins suggests that links between metabolic sensors and transcription are established directly through enzymes that participate in metabolism.

TL;DR: Efforts in this chapter hope, not only ‘conventional’ inhibitors or activators ofenzymes but also more sophisticated drugs that will direct the ubiquitin system to target, destroy and, thereby, inhibitfunctionally any specific protein.

TL;DR: Mediator was discovered because of its activity in a yeast RNA polymerase II (pol II) transcription system - it is needed for the system to respond to a transcriptional activator.

TL;DR: T theoretical and experimental findings provide strong evidence against identifying DRMs with rafts and lo domains, and functional domains in biological membranes might differ markedly from the generally accepted picture.

TL;DR: Gene-targeting studies in the mouse have recently uncovered key roles for specific PI3K isoforms in immunity, metabolism and cardiac function, and targeting strategies that take into account the complex interplay between members of thePI3K family will be crucial to gain a full understanding of the physiological roles of the isoforms of PI3k.

TL;DR: It is suggested that intrinsically unstructured proteins (IUPs) might provide radically different mechanisms that give rise to unprecedented cases of moonlighting by eliciting opposing (inhibiting and activating) action on different partners or even the same partner molecule.

TL;DR: The recent studies have begun to elucidate the substrate specificity and the mechanisms that control ADAM-mediated shedding events that regulate, for example, growth-factor and Notch signalling, and the processing of the amyloid precursor protein.

TL;DR: Emerging evidence indicates, however, that siRISC and miRISC are distinct complexes that regulate mRNA stability and translation.

TL;DR: Mammalian Mediator is a key coactivator that enables transcriptional activators to regulate transcription by RNA polymerase II (pol II) and allows for assimilation of other diverse signals such as those emanating from repressors and other coactivators.

TL;DR: The FH1 domain influences FH2 domain function through binding to the actin monomer-binding protein, profilin, and amino acid similarity between formins decreases, suggesting diverse mechanisms for regulation and cellular localization.

TL;DR: NPP-type ectophosphodiesterases are also implicated in the pathophysiology of cancer, insulin resistance and calcification diseases, and they hold great promise as easily accessible therapeutic targets.

TL;DR: This work has shown that not only are pro-survival, inflammatory and immune responses triggered by RIP kinases via the activation of transcription factors such as NF-kappaB and AP-1, but opposing, death-inducing programs can also be initiated by the RIPKinases.

TL;DR: It is suggested that a major form of negative feedback inhibition of PI3K results from activated growth signalling via mammalian target of rapamycin and the p70 S6 kinase (S6K) - a pathway that could have consequences for the development of type 2 diabetes and tuberous sclerosis complex.

TL;DR: A picture of highly organized complexes is emerging that shows that the complex that catalyzes the central steps of editing is partitioned into distinct insertion and deletion editing subcomplexes.

TL;DR: The essential character of Fe-S-protein biogenesis in eukaryotes and its importance for human disease identifies this evolutionary ancient process as one of the most important biosynthetic pathways of life.

TL;DR: The complementarity that leads to the pairing of the strands of the DNA double helix can be exploited to assemble more complex motifs, based on branched structures, to be used as the basis of larger 2D and 3D constructions.

TL;DR: The analysis of GlyT knockout mice has revealed distinct functions of individual GlyT subtypes in synaptic transmission and provided animal models for two hereditary human diseases, glycine encephalopathy and hyperekplexia, which could be of therapeutic value in cognitive disorders, schizophrenia and pain.

TL;DR: In the extensive network of interdependent biochemical processes required for cell growth and division, there is mounting evidence that ribosomal DNA transcription by RNA polymerase I (pol I) not only drives cell growth via its direct role in production of the ribosomes, but that it is also crucial in determining the fate of the cell.

TL;DR: The Saccharomyces cerevisiae Mediator was the first to be defined and is a high molecular mass complex composed of >20 distinct subunits that performs multiple activities in transcription.

TL;DR: Microarray-based methods are increasingly used to study not only transcription but also global patterns of transcript decay and translation rates in addition to comprehensively identify targets of RNA-binding proteins.

TL;DR: This data indicates that the structure of the 30S ribosomal subunit is determined by the isomorphous replacement method, which is similar to that of the H2O2 subunit determined in the study of haemoglobin.

TL;DR: Under silent conditions the antidote inhibits the toxin and the toxin-antidote complex acts as a repressor for the TA operon, whereas under conditions of activation proteolytic degradation of the antidote outpaces its synthesis.

TL;DR: Evaluation of the functional roles of individual ARSs and AIMPs might help to elucidate why these proteins as a whole contribute such varied functions and interactions in complex systems.

TL;DR: The zinc finger protein A20 was shown to exert two opposing activities: sequential de-ubiquitination and ubiquitination of the TNF receptor-interacting protein (RIP), thereby targeting RIP to proteasomal degradation.

TL;DR: To function properly, many of these processes rely on a powerful sulfur redox chemistry, which is best exemplified by the complex, newly emerging cysteine-based redox regulation of the glutathione and thioredoxin pathways.

TL;DR: Recent studies have provided accumulating evidence that has led some researchers in the field to conclude that E4, indeed, represents a distinct and novel class of enzymes.

TL;DR: Oligosaccharide chains of glycoproteins, glycolipids and glycosaminoglycans are synthesized by glycosyltransferases by the transfer of specific Glycosyl moieties from activated sugar-nucleotide donors to specific acceptors by a few residues in the sugar- nucleotide-binding pocket of the enzyme.

TL;DR: Several recently reported 3D structures of protein-LxxLL motif complexes and an intriguing novel interaction implicated in leukaemia have further highlighted the diversity and regulatory importance of this seemingly simple motif.