摘要:

AbstractThe most common form of the CO2‐fixing enzyme rubisco is a form I enzyme, heretofore found universally in oxygenic phototrophs (cyanobacteria and plastids) and widely in proteobacteria. Two groups(1–4), however, now report that in dinoflagellate plastids the usual form I rubisco has been replaced by the distantly related form II enzyme, known previously only from anaerobic proteobacteria. This raises the important question of how such an oxygensensitive rubisco could function in an aerobic organism. Moreover, the dinoflagellate rubisco has unusual molecular properties: it is encoded as a polyprotein, by nuclear (rather than plastid) genes, and these genes contain noncanonical spliceosomal introns. The nuclear location and alphaproteobacterial affinity of dinoflagellate rubisco genes hint at a possible mitochondrial origin and highlight the extraordinary richness of lateral gene transfers, both between and within organisms, that have occurred during rubisco evolut

ISSN:0265-9247    

DOI:10.1002/bies.950171202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractDefects of growth inhibitory pathways have an important role in disorders of cell growth and differentiation. The discovery of a mutation in one of the principle components of the transforming growth factor β (TGFβ) receptor system which is linked to a DNA repair defect(1)represents one possible mechanism of escape from negative regulatory influences acting upon cells. TGFβ is a pre‐eminent negative growth factor and this article discusses (1) the role of TGFβ in maintaining epithelial homeostasis; (2) how breakdown of inhibitory pathways can promote neoplastic development; (3) the significance of a receptor defect in a negative signalling pathway; and (4) the potential therapeutic sequelae resulting from restoration of cellular responsiveness to

ISSN:0265-9247    

DOI:10.1002/bies.950171203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThe N‐terminal domain of histone H4 has been implicated in various nuclear functions, including gene silencing and activation and replication‐linked chromatin assembly. Many of these have been identified by using H4 mutants in the yeastS. cerevisiae. In a recent paper, Megeeet al.(1)use this approach to show that mutants in which all four N‐terminal H4 lysines are substituted with glutamines accumulate increased levels of DNA damage. A single lysine, but not an arginine, anywhere in the N‐terminal domain suppresses this phenotype. It is suggested that histone H4 plays a role in maintaining genome integrity through the cell cycle, possibly by a mechanism involving lysine acet

ISSN:0265-9247    

DOI:10.1002/bies.950171204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractCancer is one of the most frequent fatal human diseases. It is a genetic disease, and molecular analysis of the genes involved revealed that they belong to several distinct classes of molecules, one of which is the receptor tyrosine kinases. Neoplastic transformation is regarded as the result of a multistep process and, in most cases, it is hard to evaluate what the initial events in tumor formation are. What makes it difficult to approach this question is the paucity of animal models for tumorigenesis allowing investigation of the mechanisms leading to uncontrolled cell proliferation. Melanoma formation in Xiphophorus is one of these model systems. Here, overexpression and activation of a receptor tyrosine kinase causes neoplastic transformation of pigment cells. Xiphophorus provides all the advantages of a well‐characterised genetic system. In addition, some crucial components of the transformation pathway have been identified at the molecular level. As a vertebrate, Xiphophorus might serve as a model system to aid understanding, in more general terms, of the mechanisms of tumorigenesis in human disease

ISSN:0265-9247    

DOI:10.1002/bies.950171205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractPhage DNA packaging occurs by DNA translocation into a prohead. Terminases are enzymes which initiate DNA packaging by cutting the DNA concatemer, and they are closely fitted structurally to the portal vertex of the prohead to form a ‘packasome’. Analysis among a number of phages supports an active role of the terminases in coupling ATP hydrolysis to DNA translocation through the portal. In phage T4 the small terminase subunit promotes a sequence‐specific terminase gene amplification within the chromosome. This link between recombination and packaging suggests a DNA synapsis mechanism by the terminase to control packaging initiation, formally homologous to eukaryotic chromosome segreg

ISSN:0265-9247    

DOI:10.1002/bies.950171206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractDiscovery of a second, inducible prostaglandin synthase provides explanations for many previously puzzling observations, but also raises new questions about prostanoid synthesis. Acis‐acting sequence closely related to the cyclic AMP response element has been shown to play a role in both basal and induced prostaglandin synthase 2 gene expression. Aspirin and other currently available non‐steroidal anti‐inflammatory drugs that inhibit prostaglandin synthase activity do not effectively discriminate between the inducible prostaglandin synthase 2 and constitutive prostaglandin synthase 1 enzymes. Identification of a second prostaglandin synthase, induced by inflammatory stimuli, initiated a search for isoform‐specific inhibitors. Use of prostaglandin synthase 2 specific inhibitors and antisense oligonucleotides has led to the suggestion that specific ligands activate alternative pathways of prostanoid production, using one of the prostaglandin synthase isoforms preferentially. The coupling mechanisms by which these pathways are activated in response to alternative stimuli should provide additional routes of intervention in prostanoid pro

ISSN:0265-9247    

DOI:10.1002/bies.950171207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractChondrocytes are specialised cells which produce and maintain the extracellular matrix of cartilage, a tissue that is resilient and pliant.In vivo, it has to withstand very high compressive loads, and that is explicable in terms of the physico‐chemical properties of cartilage‐specific macromolecules and with the movement of water and ions within the matrix. The functions of the cartilage‐specific collagens, aggrecan (a hydrophilic proteoglycan) and hyaluronan are discussed within this context. The structures of cartilage collagens and proteoglycans and their genes are known and a number of informative mutations have been identified. In particular, collagen fibrillogenesis is a complex process which can be altered by mutations whose effects fit what is known about collagen molecular structural functions. In other instances, mutations have indicated new functions for particular molecular domains. As cartilage provides the template for the developing skeleton, mutations in genes for cartilage‐specific proteins often produce developmental abnormalities. The search for mutations amongst such genes in heritable disorders is being actively pursued by many groups, although mutation and phenotype are not always well correlated, probably because of compensatory mechanisms. The special nature of the chondrocyte is stressed in connection with its cell involvement in osteoarthritis, the most widespread disease of diarthrodial

ISSN:0265-9247    

DOI:10.1002/bies.950171208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractMost lymphocytes of the T cell lineage develop along the CD4/CD8 pathway and express antigen receptors on their surfaces consisting of clonotypic αβ chains associated with invariant CD3‐γδε components and ζ chains, collectively referred to as the T cell antigen receptor complex (TCR). Expression of the TCR complex is dynamically regulated during T cell development, with immature CD4+CD8+thymocytes expressing only 10% of the number of αβ TCR complexes on their surfaces expressed by mature CD4+and CD8+T cells. Recent evidence demonstrates that low surface TCR density on CD4+CD8+thymocytes results from the limited survival of a single TCR component within the ER, the TCRα chain, which has a half life of only 15 minutes in immature thymocytes, compared to>75 minutes in mature T cells. Instability of TCRα proteins in immature CD4+CD8+thymocytes represents a novel mechanism by which expression of the multisubunit TCR complex is quantitatively regulated during T cell development. In the current review we discuss our recent findings concerning the assembly, intracellular transport, and expression of αβ TCR complexes in CD4+CD8+thymocytes and comment on the functional significance of TCRα instability during T ce

ISSN:0265-9247    

DOI:10.1002/bies.950171209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractSpecific inhibition of gene expression by antisense agents provides the basis for rational drug discovery based on molecular targets. Due to the specificity of Watson‐Crick base‐pair hybridization, antisense oligodeoxynucleotides have been used extensively in attempts to inhibit gene expression in bothin vitroandin vivomodels. Analogues modified from normal phosphodiester oligodeoxynucleotides have entered clinical trials against diseases including AIDS and cancer. Although the precise mechanism of action of these drugs has not been clarified, these oligodeoxynucleotides offer considerable promise as novel molecular therapeutics. We review the recent attempts to harness the therapeutic potential of these oligodeoxynucleotides and appraise the near‐term prospects for antisense techn

ISSN:0265-9247    

DOI:10.1002/bies.950171210

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractIn the minds of many,Hoxgene null mutant phenotypes have confirmed the direct role that these genes play in specifying the pattern of vertebrate embryos. The genes are envisaged as defining discrete spatial domains and, subsequently, conferring specific segmental identities on cells undergoing differentiation along the antero‐posterior axis. However, several aspects of the observed mutant phenotypes are inconsistent with this view. These include: the appearance of other, unexpected transformations along the dorsal axis; the occurrence of mirror‐image duplications; and the development of anomalies outside the established domains of normalHoxgene expression. In this paper,Hoxgene disruptions are shown to elicit regeneration‐like responses in tissues confronted with discontinuities in axial identity. The polarities and orientations of transformed segments which emerge as a consequence of this response obey the rules of distal transformation and intercalary regeneration. In addition, the incidence of periodic anomalies suggests that the initial steps ofHox‐mediated patterning occurs in Hensen's node. As gastrulation proceeds, mesoderm cell cycle kinetics impose constraints upon subsequent cellular differentiation. This results in the delayed manifestation of transformations along the antero‐posterior axis. Finally, a paradigm is sketched in which temporal, rather than spatial axial determinants direct differentiation. Specific, testable predictions are made about the role ofHoxgenes in the establishment of segmental

ISSN:0265-9247    

DOI:10.1002/bies.950171211

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY