| 1. |
- Aspenström, Pontus, et al.
(författare)
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Pombe Cdc15 homology proteins : regulators of membrane dynamics and the actin cytoskeleton
- 2006
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Ingår i: TIBS -Trends in Biochemical Sciences. Regular ed.. - : Elsevier BV. - 0968-0004 .- 1362-4326. ; 31:12, s. 670-679
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Forskningsöversikt (refereegranskat)abstract
- Pombe Cdc15 homology (PCH) proteins have emerged in many species as important coordinators of signalling pathways that regulate actomyosin assembly and membrane dynamics. For example, the prototype PCH protein, Cdc15p of Schizosaccharomyces pombe, has a role in assembly of the contractile ring, which is needed to separate dividing cells. Recently, mammalian PCH proteins have been found to bind phospholipids and to participate in membrane deformation. These findings suggest that PCH proteins are crucial linkers of membrane dynamics and actin polymerization, for example, during the internalization of transmembrane receptors. Intriguingly, some members of the PCH protein family are mutated in neurodegenerative and inflammatory diseases, which has implications for the identification of cures for such disorders.
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| 2. |
- Björklund, Stefan, et al.
(författare)
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Mediator of transcriptional regulation.
- 1996
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Ingår i: TIBS -Trends in Biochemical Sciences. Regular ed.. - 0968-0004 .- 1362-4326. ; 21:9, s. 335-7
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Tidskriftsartikel (refereegranskat)abstract
- A multi-protein complex, termed mediator, has been isolated from yeast, based on its requirement for transcriptional activation in a system reconstituted from pure RNA polymerase II and general transcription factors. Mediator polypeptides include the products of many genes previously recovered from screens for mutations affecting transcription. This connection between biochemical and genetic studies reveals that mediator is important for both activation and repression of transcription, and that mediator plays a role in transcriptional regulation in vivo as well as in vitro. Mediator binds the carboxy-terminal domain of RNA polymerase II, forming a polymerase holoenzyme, whose possible association with additional proteins is a subject of some controversy.
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| 3. |
- Carnevale, Vincenzo, et al.
(författare)
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Molecular Dynamics Simulations of Ion Channels
- 2021
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Ingår i: TIBS -Trends in Biochemical Sciences. Regular ed.. - : Elsevier BV. - 0968-0004 .- 1362-4326. ; 46:7, s. 621-622
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Cerenius, Lage, et al.
(författare)
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Proteolytic cascades and their involvement in invertebrate immunity
- 2010
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Ingår i: TIBS -Trends in Biochemical Sciences. Regular ed.. - : Elsevier BV. - 0968-0004 .- 1362-4326. ; 35:10, s. 575-583
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Forskningsöversikt (refereegranskat)abstract
- Bacteria and other potential pathogens are cleared rapidly from the body fluids of invertebrates by the immediate response of the innate immune system. Proteolytic cascades, following their initiation by pattern recognition proteins, control several such reactions, notably coagulation, melanisation, activation of the Toll receptor and complement-like reactions. However, there is considerable variation among invertebrates and these cascades, although widespread, are not present in all phyla. In recent years, significant progress has been made in identifying and characterizing these cascades in insects. Notably, recent work has identified several connections and shared principles among the different pathways, suggesting that cross-talk between them may be common.
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| 5. |
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| 6. |
- Davies, James S., et al.
(författare)
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TRAPs : the 'elevator-with-an-operator' mechanism
- 2024
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Ingår i: Trends in Biochemical Sciences (TIBS). - 0968-0004 .- 1362-4326. ; 49:2, s. 134-144
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Forskningsöversikt (refereegranskat)abstract
- Tripartite ATP -independent periplasmic (TRAP) transporters are nutrient -uptake systems found in bacteria and archaea. These evolutionary divergent transporter systems couple a substrate -binding protein (SBP) to an elevator -type secondary transporter, which is a first -of -its -kind mechanism of transport. Here, we highlight breakthrough TRAP transporter structures and recent functional data that probe the mechanism of transport. Furthermore, we discuss recent structural and biophysical studies of the ion transporter superfamily (ITS) members and highlight mechanistic principles that are relevant for further exploration of the TRAP transporter system.
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| 7. |
- Deindl, Sebastian, et al.
(författare)
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More Than Just Letters and Chemistry : Genomics Goes Mechanics
- 2021
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Ingår i: TIBS -Trends in Biochemical Sciences. Regular ed.. - : Elsevier. - 0968-0004 .- 1362-4326. ; 46:6, s. 431-432
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Although ubiquitously thought of as a simple string of letters, DNA exhibits complex physicochemical properties. As a result, DNA can store information beyond the extensively studied explicit genetic message. The mechanical code of DNA has not been studied systematically in a genome-wide context until recent groundbreaking work by Basu et al.
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| 8. |
- Gianni, Stefano, et al.
(författare)
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How Fast Is Protein-Ligand Association?
- 2017
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Ingår i: TIBS -Trends in Biochemical Sciences. Regular ed.. - : Elsevier BV. - 0968-0004 .- 1362-4326. ; 42:11, s. 847-849
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- There is increasing interest in studying protein interactions and their role in cell biology using kinetics. However, there is confusion about the proper terminology in terms of the distinction between rates and rate constants. We recommend a more stringent use of the words speed, fast, slow, rate, and rate constant.
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| 9. |
- Grosjean, Henri, et al.
(författare)
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Aminoacylation of the anticodon stem by a tRNA-synthetase paralog : relic of an ancient code?
- 2004
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Ingår i: TIBS -Trends in Biochemical Sciences. Regular ed.. - London : Elsevier. - 0968-0004 .- 1362-4326. ; 29:10, s. 519-522
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Tidskriftsartikel (refereegranskat)abstract
- The activation and charging of amino acids onto the acceptor stems of their cognate tRNAs are the housekeeping functions of aminoacyl-tRNA synthetases. The availability of whole genome sequences has revealed the existence of synthetase-like proteins that have other functions linked to different aspects of cell metabolism and physiology. In eubacteria, a paralog of glutamyl tRNA synthetase, which lacks the tRNA-binding domain, was found to aminoacylate tRNA(Asp) not on the 3'-hydroxyl group of the acceptor stem but on a cyclopentene diol of the modified nucleoside queuosine present at the wobble position of anticodon loop. This modified nucleoside might be a relic of an ancient code.
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| 10. |
- Grosjean, Henri, et al.
(författare)
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Enzymatic conversion of cytidine to lysidine in anticodon of bacterial isoleucyl-tRNA--an alternative way of RNA editing
- 2004
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Ingår i: TIBS -Trends in Biochemical Sciences. Regular ed.. - Amsterdam : Int. union of biochemistry and Elsevier/North-Holland. - 0968-0004 .- 1362-4326. ; 29:4, s. 165-168
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Tidskriftsartikel (refereegranskat)abstract
- In most organisms, the AUA triplet codes for isoleucine (Ile), whereas in a few organelles it codes for methionine (Met). In bacteria, this A-ending triplet is decoded by an unusual tRNA harboring a Met anticodon CAU, where cytidine at the wobble position 34 (C34) is posttranscriptionally modified to a 2-lysyl cytidine (lysidine), abbreviated as (k2C). Now, the bacterial gene tilS, which encodes the enzyme catalyzing the lysylation of C34 in the precursor tRNAIle(CAU), thereby leading to the formation of tRNAIle(k2CAU), has been identified. The formation of lysidine by this essential enzyme allows recognition of tRNAIle(k2CAU) by Ile-tRNA synthetase and switches the base pairing of the tRNA from AUG (Met) to AUA (Ile). This base change is reminiscent of C-to-U type of RNA editing of some mitochondrial tRNAs.
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| 11. |
- Johansson, Erik, et al.
(författare)
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The eukaryotic replicative DNA polymerases take shape.
- 2010
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Ingår i: TIBS -Trends in Biochemical Sciences. Regular ed.. - : Elsevier. - 0968-0004 .- 1362-4326. ; 35:6, s. 339-347
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Forskningsöversikt (refereegranskat)abstract
- Three multi-subunit DNA polymerase enzymes lie at the heart of the chromosome replication machinery in the eukaryotic cell nucleus. Through a combination of genetic, molecular biological and biochemical analysis, significant advances have been made in understanding the essential roles played by each of these enzymes at the replication fork. Until very recently, however, little information was available on their three-dimensional structures. Lately, a series of crystallographic and electron microscopic studies has been published, allowing the structures of the complexes and their constituent subunits to be visualised in detail for the first time. Taken together, these studies provide significant insights into the molecular makeup of the replication machinery in eukaryotic cells and highlight a number of key areas for future investigation.
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| 12. |
- Lee, Dung-Fang, et al.
(författare)
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ZNF217/ZFP217 Meets Chromatin and RNA
- 2016
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Ingår i: Trends in Biochemical Sciences (TIBS). - : Elsevier. - 0968-0004 .- 1362-4326. ; 41:12, s. 986-988
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Tidskriftsartikel (refereegranskat)abstract
- The Kruppel-like transcription factor zinc finger protein (ZNF)217 (mouse homolog ZFP217) contributes to tumorigenesis by dysregulating gene expression programs. The newly discovered molecular function of ZFP217 in controlling N6-methyladenosine (m6A) deposition in embryonic stem cells (ESCs) sheds new light on the role of this transcription factor in tumor development.
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| 13. |
- Lönn, Peter, et al.
(författare)
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Close Encounters : Probing Proximal Proteins in Live or Fixed Cells
- 2017
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Ingår i: TIBS -Trends in Biochemical Sciences. Regular ed.. - : Elsevier BV. - 0968-0004 .- 1362-4326. ; 42:7, s. 504-515
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Forskningsöversikt (refereegranskat)abstract
- The well-oiled machinery of the cellular proteome operates via variable expression, modifications, and interactions of proteins, relaying genomic and transcriptomic information to coordinate cellular functions. In recent years, a number of techniques have emerged that serve to identify sets of proteins acting in close proximity in the course of orchestrating cellular activities. These proximi dependent assays, including BiFC, BioID, APEX, FRET, and isPLA, have opened up new avenues to examine protein interactions in live or fixed cells. We review herein the current status of proximity-dependentin situ techniques. We compare the advantages and limitations of the methods, underlining recent progress and the growing importance of these techniques in basic research, and we discuss their potential as tools for drug development and diagnostics.
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| 14. |
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| 15. |
- Montero, Olimpio, et al.
(författare)
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Trials and tribulations of statistical significance in biochemistry and omics
- 2023
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Ingår i: TIBS -Trends in Biochemical Sciences. Regular ed.. - : Elsevier. - 0968-0004 .- 1362-4326. ; 48:6, s. 503-512
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Over recent years many statisticians and researchers have highlighted that statis-tical inference would benefit from a better use and understanding of hypothesis testing, p-values, and statistical significance. We highlight three recommendations in the context of biochemical sciences. First recommendation: to improve the bio-logical interpretation of biochemical data, do not use p-values (or similar test statis-tics) as thresholded values to select biomolecules. Second recommendation: to improve comparison among studies and to achieve robust knowledge, perform complete reporting of data. Third recommendation: statistical analyses should be reported completely with exact numbers (not as asterisks or inequalities). Owing to the high number of variables, a better use of statistics is of special importance in omic studies.
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| 16. |
- Nilsson, Avlant, 1985, et al.
(författare)
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Metabolite Depletion Affects Flux Profiling of Cell Lines
- 2018
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Ingår i: Trends in Biochemical Sciences. - : Elsevier BV. - 1362-4326 .- 0968-0004. ; 43:6, s. 395-397
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Quantifying the rate of consumption and release of metabolites (i.e., flux profiling) has become integral to the study of cancer. The fluxes as well as the growth of the cells may be affected by metabolite depletion during cultivation.
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| 17. |
- Pinto, Gaspar P., et al.
(författare)
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Exploiting enzyme evolution for computational protein design
- 2022
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Ingår i: TIBS -Trends in Biochemical Sciences. Regular ed.. - : Elsevier. - 0968-0004 .- 1362-4326. ; 47:5, s. 375-389
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Forskningsöversikt (refereegranskat)abstract
- Recent years have seen an explosion of interest in understanding the physicochemical parameters that shape enzyme evolution, as well as substantial advances in computational enzyme design. This review discusses three areas where evolutionary information can be used as part of the design process: (i) using ancestral sequence reconstruction (ASR) to generate new starting points for enzyme design efforts; (ii) learning from how nature uses conformational dynamics in enzyme evolution to mimic this process in silico; and (iii) modular design of enzymes from smaller fragments, again mimicking the process by which nature appears to create new protein folds. Using showcase examples, we highlight the importance of incorporating evolutionary information to continue to push forward the boundaries of enzyme design studies.
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| 18. |
- Sanchez, M. Florencia, et al.
(författare)
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Presenting technological workflows
- 2023
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Ingår i: TIBS -Trends in Biochemical Sciences. Regular ed.. - : Cell Press. - 0968-0004 .- 1362-4326. ; 48:7, s. 587-589
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 19. |
- Simonetti, Leandro, et al.
(författare)
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SLiM-binding pockets : an attractive target for broad-spectrum antivirals
- 2023
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Ingår i: TIBS -Trends in Biochemical Sciences. Regular ed.. - : Elsevier. - 0968-0004 .- 1362-4326. ; 48:5, s. 420-427
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Forskningsöversikt (refereegranskat)abstract
- Short linear motif (SLiM)-mediated interactions offer a unique strategy for viral intervention due to their compact interfaces, ease of convergent evolution, and key functional roles. Consequently, many viruses extensively mimic host SLiMs to hijack or deregulate cellular pathways and the same motif-binding pocket is often targeted by numerous unrelated viruses. A toolkit of therapeutics targeting commonly mimicked SLiMs could provide prophylactic and therapeutic broadspectrum antivirals and vastly improve our ability to treat ongoing and future viral outbreaks. In this opinion article, we discuss the therapeutic relevance of SLiMs, advocating their suitability as targets for broad-spectrum antiviral inhibitors.
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| 20. |
- van der Oost, John, et al.
(författare)
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CRISPR-based adaptive and heritable immunity in prokaryotes
- 2009
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Ingår i: TIBS -Trends in Biochemical Sciences. Regular ed.. - : Elsevier BV. - 0968-0004 .- 1362-4326. ; 34:8, s. 401-407
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Forskningsöversikt (refereegranskat)abstract
- The recently discovered CRISPR (clustered regularly interspaced short palindromic repeat) defense system protects bacteria and archaea against mobile genetic elements. This immunity system has the potential to continuously adjust its reach at the genomic level, implying that both gain and loss of information is inheritable. The CRISPR system consists of typical stretches of interspaced repetitive DNA (CRISPRs) and associated cas genes. Three distinct stages are recognized in the CRISPR defense mechanism: (i) adaptation of the CRISPR via the integration of short sequences of the invaders as spacers; (ii) expression of CRISPRs and subsequent processing to small guide RNAs; and (iii) interference of target DNA by the crRNA guides. Recent analyses of key Cas proteins indicate that, despite some functional analogies, this fascinating prokaryotic system shares no phylogenetic relation with the eukaryotic RNA interference system.
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| 21. |
- Zhang, Long, et al.
(författare)
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Signaling interplay between transforming growth factor-beta receptor and PI3K/AKT pathways in cancer
- 2013
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Ingår i: TIBS -Trends in Biochemical Sciences. Regular ed.. - : Elsevier BV. - 0968-0004 .- 1362-4326. ; 38:12, s. 612-620
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Forskningsöversikt (refereegranskat)abstract
- The transforming growth factor (TGF)-beta and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathways are used in cells to control numerous responses, including proliferation, apoptosis, and migration. TGF-beta is known for its cytostatic effect's in premalignant states and its pro-oncogenic activity in advanced cancers. The pro-cell survival response exerted by growth-factor-mediated activation of PI3K/AKT has been linked to stimulation of tumor formation. Both TGF-beta receptor and PI3K/AKT pathways were initially modeled as linear signaling conduits. Although early studies suggested that these two pathways might counteract each other in balancing cell survival, emerging evidence has uncovered multiple modes of intricate signal integration and obligate collaboration in driving cancer progression. These new insights provide the rationale for exploring their dual targeting in cancer.
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| 22. |
- Zhou, Xingchen, et al.
(författare)
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UFMylation: a ubiquitin-like modification
- 2024
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Ingår i: Trends in Biochemical Sciences. - 0968-0004 .- 1362-4326. ; 49:1, s. 52-67
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Forskningsöversikt (refereegranskat)abstract
- Post-translational modifications (PTMs) add a major degree of complexity to the proteome and are essential controllers of protein homeostasis. Amongst the hundreds of PTMs identified, ubiquitin and ubiquitin-like (UBL) modifications are recognized as key regulators of cellular processes through their ability to affect protein–protein interactions, protein stability, and thus the functions of their protein targets. Here, we focus on the most recently identified UBL, ubiquitin-fold modifier 1 (UFM1), and the machinery responsible for its transfer to substrates (UFMylation) or its removal (deUFMylation). We first highlight the biochemical peculiarities of these processes, then we develop on how UFMylation and its machinery control various intertwined cellular processes and we highlight some of the outstanding research questions in this emerging field.
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| 23. |
- Akerström, B, et al.
(författare)
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An intriguing member of the lipocalin protein family : alpha 1-microglobulin
- 1990
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Ingår i: Trends in Biochemical Sciences. - 0968-0004. ; 15:6, s. 3-240
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Forskningsöversikt (refereegranskat)abstract
- The plasma protein alpha 1-microglobulin is a member of the lipocalin protein superfamily. In the last few years, the work on alpha 1-microglobulin has given unexpected and promising new results. Of particular interest are its molecular association with immunoglobulin A and with proteinase inhibitors, and its interactions with the immune system.
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| 24. |
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| 25. |
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| 26. |
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Yakovleva, T, et al.
(författare)
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p53 latency--out of the blind alley
- 2002
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Ingår i: Trends in biochemical sciences. - 0968-0004. ; 27:12, s. 612-618
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Tidskriftsartikel (refereegranskat)
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| 31. |
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| 32. |
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| 33. |
- Al-Karadaghi, Salam, et al.
(författare)
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Chelatases: distort to select?
- 2006
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Ingår i: Trends in Biochemical Sciences. - : Elsevier BV. - 0167-7640 .- 0968-0004. ; 31:3, s. 135-142
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Chelatases catalyze the insertion of a specific metal ion into porphyrins, a key step in the synthesis of metalated tetrapyrroles that are essential for many cellular processes. Despite apparent common structural features among chelatases, no general reaction mechanism accounting for metal ion specificity has been established. We propose that chelatase-induced distortion of the porphyrin substrate not only enhances the reaction rate by decreasing the activation energy of the reaction but also modulates which divalent metal ion is incorporated into the porphyrin ring. We evaluate the recently recognized interaction between ferrochelatase and frataxin as a way to regulate iron delivery to ferrochelatase, and thus iron and heme metabolism. We postulate that the ferrochelatase-frataxin interaction controls the type of metal ion that is delivered to ferrochelatase.
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| 34. |
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| 35. |
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| 36. |
- Carlsten, Jonas O P, et al.
(författare)
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The multitalented Mediator complex
- 2013
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Ingår i: Trends in Biochemical Sciences. - : Elsevier BV. - 0968-0004. ; 38:11, s. 531-537
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Tidskriftsartikel (refereegranskat)abstract
- The Mediator complex is needed for regulated transcription of RNA polymerase II (Pol II)-dependent genes. Initially, Mediator was only seen as a protein bridge that conveyed regulatory information from enhancers to the promoter. Later studies have added many other functions to the Mediator repertoire. Indeed, recent findings show that Mediator influences nearly all stages of transcription and coordinates these events with concomitant changes in chromatin organization. We review the multitude of activities associated with Mediator and discuss how this complex coordinates transcription with other cellular events. We also discuss the inherent difficulties associated with in vivo characterization of a coactivator complex that can indirectly affect diverse cellular processes via changes in gene transcription.
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Hangen, Emilie, et al.
(författare)
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Life with or without AIF.
- 2010
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Ingår i: Trends in biochemical sciences. - : Elsevier BV. - 0968-0004. ; 35:5, s. 278-87
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Forskningsöversikt (refereegranskat)abstract
- Apoptosis-inducing factor (AIF) was initially discovered as a caspase-independent death effector. AIF fulfills its lethal function after its release from mitochondria and its translocation to the nucleus of the dying cell. The contribution of AIF to programmed cell death is dependent upon the cell type and apoptotic insult. Recent in vivo data indicate that, in addition to its lethal activity, AIF plays a vital mitochondrial role in healthy cells. A segment of AIF which is dispensable for its apoptotic function carries an NADH-oxidase domain that regulates the respiratory chain complex I and is required for cell survival, proliferation and mitochondrial integrity. Mice that express reduced levels of AIF constitute a reliable model of complex I deficiency. Here we discuss recent reports on the survival-related function(s) of AIF.
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| 41. |
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| 42. |
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| 43. |
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| 44. |
- Massoumi, Ramin
(författare)
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Ubiquitin chain cleavage: CYLD at work.
- 2010
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Ingår i: Trends in Biochemical Sciences. - : Elsevier BV. - 0167-7640 .- 0968-0004. ; 35, s. 392-399
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Tidskriftsartikel (refereegranskat)abstract
- The tumor suppressor CYLD is a deubiquitylating enzyme that negatively regulates different signaling pathways by removing lysine 63-linked polyubiquitin chains from several specific substrates. In various tumor types, CYLD loss can lead to cell survival or cell proliferation. In addition to its loss due to mutations, CYLD expression can also be decreased through transcriptional and post-transcriptional regulatory mechanisms. Moreover, as epigenetic repression of CYLD can affect tumor progression in different cancer types, the activation of the CYLD promoter ensures the tight control of an inflammatory response. Recent work also shows that CYLD activity can be governed by different regulatory mechanisms including phosphorylation, thus providing another layer of control for diverse physiological processes.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Nicholls, Thomas J., et al.
(författare)
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Separating and Segregating the Human Mitochondrial Genome
- 2018
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Ingår i: Trends in Biochemical Sciences. - : Elsevier BV. - 0968-0004. ; 43:11, s. 869-881
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Tidskriftsartikel (refereegranskat)abstract
- Cells contain thousands of copies of the mitochondrial genome. These genomes are distributed within the tubular mitochondrial network, which is itself spread across the cytosol of the cell. Mitochondrial DNA (mtDNA) replication occurs throughout the cell cycle and ensures that cells maintain a sufficient number of mtDNA copies. At replication termination the genomes must be resolved and segregated within the mitochondrial network. Defects in mtDNA replication and segregation are a cause of human mitochondrial disease associated with failure of cellular energy production. This review focuses upon recent developments on how mitochondrial genomes are physically separated at the end of DNA replication, and how these genomes are subsequently segregated and distributed around the mitochondrial network.
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| 49. |
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| 50. |
- Rydström, Jan, 1943
(författare)
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Mitochondrial transhydrogenase--a key enzyme in insulin secretion and, potentially, diabetes.
- 2006
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Ingår i: Trends in biochemical sciences. - : Elsevier BV. - 0968-0004. ; 31:7, s. 355-8
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Tidskriftsartikel (refereegranskat)abstract
- Two recent studies have shown that the glucose intolerance and impaired insulin secretion of the C57BL/6J mouse strain results from oxidative stress due to a mutated nicotinamide nucleotide transhydrogenase. Reproduction of this phenotype, by mutating the same enzyme in another strain with normal glucose tolerance, suggests that the mechanism of the transhydrogenase-dependent inhibition of insulin secretion involves a partial uncoupling by the UCP2 protein. These exciting findings raise important questions, not least their potential relevance for human diabetes.
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