摘要:

AbstractThree apparently unrelated developmental processes – mammalian myogenesis, the choice of neural fate and sex determination inDrosophila– are controlled by a common mechanism. Most of the genes governing these processes encode transcriptional factors that contain the helix‐loop‐helix (HLH) motif. This domain mediates the formation of homo‐ or heterodimers that specifically bind to DNA through a conserved basic region adjacent to the HLH motif. Dimers differ in their affinity for DNA and in their ability to activate transcription from HLH binding‐site containing promoters. In addition, the activity of HLH proteins is inhibited by dimerization with another class of HLH proteins that lack a basic domain entirely or have an altered one. These structural properties provide a molecular mechanism to explain the synergistic and antagonistic functional relations among the HLH encoding genes that control several development

ISSN:0265-9247    

DOI:10.1002/bies.950131002

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

年代:1991

数据来源: WILEY

摘要:

AbstractConsistent with the complexity of the temporally regulated processes that must occur for growth and development of higher eukaryotes, it is now apparent that transcription is regulated by the formation of multi‐component complexes that assemble on the promoters of genes. These complexes can include (in addition to the five or more general transcription factors and RNA polymerase II) DNA‐binding proteins, transcriptional activators, coactivators, adaptors and various accessory proteins. The best studied example of a complex that includes a transcriptional adaptor, accessory proteins and a DNA‐binding protein is that involving the herpes simplex virus VP16 protein. Evidence suggests that the adenovirus E1a protein and the cellular Sp1 and CTF/NF1 transcription factors also function through adaptors or coactivators. Each additional component of the transcription complex provides the cell with another point at which to exert control of gene expre

ISSN:0265-9247    

DOI:10.1002/bies.950131003

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

年代:1991

数据来源: WILEY

摘要:

AbstractExpression patterns ofAntennapedia‐like homeogenes in the mouse embryo show many similarities to those of their homologues inDrosophila. It is argued here that homeogenes may regulate development of the body plan in mouse by mechanisms similar to those used inDrosophila.In particular, they may differentially specify positional address of cell groups within lineage compartments along the body axes. In vertebrates, a single ancestral homeogene cluster has become duplicated to give four separate clusters. Comparisons of homeogene expression patterns between different clusters of the mouse suggest ways in which duplication has permitted development of a more complex body plan. Cluster duplication may therefore have provided a selective advantage during vertebrate evolutio

ISSN:0265-9247    

DOI:10.1002/bies.950131004

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

年代:1991

数据来源: WILEY

摘要:

AbstractA set of amino acid side chains that confer specificity for the coenzyme NADPH and the substrate glutathione in the flavoprotein disulphide oxidoreductase, glutathione reductase, has been identified. Systematic replacement of these amino acid residues in the coenzyme‐binding site switches the specificity of the enzyme from its natural strong preference for NADPH to a marked preference For NADH. The amino acids replaced all lie in a structural motif within the dinucleotide‐binding domain of the protein. Since this domain is a feature common to most dehydrogenases (reductases) that use nicotinamide coenzymes, it may be that the coenzyme specificities of all such enzymes can be manipulated in this way. Similarly, amino acid residues involved in the selective recognition of trypanothione by trypanothione reductase, an enzyme related to glutathione reductase and exclusive to trypanosomatids, were identified. Suitable mutation of the corresponding residues inE. coliglutathione reductase switched its substrate specificity towards trypanothione. A better understanding of the substrate specificity of these enzymes could open up a route to the chemotherapy of trypanosomal infecti

ISSN:0265-9247    

DOI:10.1002/bies.950131005

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

年代:1991

数据来源: WILEY

摘要:

AbstractFibronectin (FN) is a multi‐functional extracellular matrix protein required for cell adhesion and migration, blood clotting, wound healing, and oncogenic transformation. The functional complexity is paralleled by structural diversity in that multiple forms of FN are generated by cell type‐specific alternative splicing. In the rat, up to 12 different combinations of the three alternatively spliced segments (EIIIA, EIIIB, and the V region) are produced. What effects do these segments have on FN function? Recently, progress has been made in the identification of specific activities for the three Variants of the V region, V120, V95, and V0. FN‐mediated cell adhesion, FN synthesis and secretion, and incorporation into blood clots are differentially affected by these isoforms. These results suggest that cellular behavior is modulated by environmental cues provided by different types and proportions of alternatively spliced FN var

ISSN:0265-9247    

DOI:10.1002/bies.950131006

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

年代:1991

数据来源: WILEY

摘要:

AbstractMouse pre‐implantation development appears to be under the control of paracrine and autocrine growth factors. The epithelium of the oviduct and the uterus together, with the population of macrophages and lymphocytes present in the reproductive tract from the onset of pregnancy, are thought to be the major sources of paracrine growth factors targeted to the developing embryos. Some of the growth factors are synthesized by both uterine epithelial cells and activated lympho‐hematopoietic cells, suggesting a partial overlap of the regulatory signals used by the reproductive and lympho‐hematopoietic systems. Such growth factors may be the long sought‐after mediators of the synchrony between the pre‐implantation embryo and the sex‐steroid hormone‐induced changes

ISSN:0265-9247    

DOI:10.1002/bies.950131007

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

年代:1991

数据来源: WILEY

ISSN:0265-9247    

DOI:10.1002/bies.950131008

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

年代:1991

数据来源: WILEY

摘要:

AbstractHuman DNA can be cloned as yeast artificial chromosomes (YACs), each of which contains several hundred kilobases of human DNA. This DNA can be manipulated in the yeast host using homologous recombination and yeast selectable markers. In relatively few steps it is possible to make virtually any change in the cloned human DNA from single base pair changes to deletions and insertions. In order to study the function of the cloned DNA and the effects of the changes made in the yeast, the human DNA must be transferred back into mammalian cells. Recent experiments indicate that large genes can be transferred from the yeast host to mammalian cells in tissue culture and that the genes are transferred intact and are expressed. Using the same methods it may soon be possible to transfer YAC DNA into the mouse germ line so that the expression and function of genes cloned in YACs can be studied in developing and adult mammalian animals.

ISSN:0265-9247    

DOI:10.1002/bies.950131009

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe major cause of death from cancer is the relentless growth of metastases that are resistant to conventional therapy. The pathogenesis of a metastasis is complex and requires that tumor cells complete a sequence of potentially lethal interactions with various host factors. The finding in 1973 that metastasis is selective process and the finding in 1977 that malignant neoplasms are heterogeneous and contain few preexisting metastatic subpopulations have added a new dimension to our understanding of cancer and its spread. This understanding is now contributing to the design of better therapies against disseminated metastasis.

ISSN:0265-9247    

DOI:10.1002/bies.950131010

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

年代:1991

数据来源: WILEY

ISSN:0265-9247    

DOI:10.1002/bies.950131011

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

年代:1991

数据来源: WILEY