BioEssays

doi: 10.1002/bies.950180101pmid: N/A

Bard, Jonathan B. L.

doi: 10.1002/bies.950180102pmid: N/A

Holliday, Robin

doi: 10.1002/bies.950180103pmid: 8593161

The replication of linear chromosome DNA by DNA polymerase leads to the loss of terminal sequences, in the absence of a special mechanism to maintain ends or telomeres. This mechanism is known to consist of short terminal repeats and the enzyme telomerase, which contains RNA complementary to the DNA repeats. There is evidence that telomeric DNA continually decreases in size in the absence of telomerase, and this is followed by cellular senescence. Immortalisation of somatic cells is accompanied, at least in some cases, by acquisition of telomerase activity. The cloning of DNA coding for the RNA component of telomerase has opened up some new experimental approaches, including the study of telomerases with mutant RNA(1,2). The telomere theory of cellular senescence appears to provide a molecular basis for the ‘Hayflick limit’ to human fibroblast growth. However the telomeres and behaviour of primary mouse cells are anomolous(3), and many immortalised human cell lines lack normal telomerase activity(4). These exceptions are not easily accommodated in the telomere theory.

Schmidt, Emmett V.

doi: 10.1002/bies.950180104pmid: 8593165

Two recent reports of mice homozygously deleted for cyclin D1 provide unequivocal evidence that the critical G1 cyclin, cyclin D1, is by itself rate‐limiting for growth in some mammalian tissues(1,2). Cyclin D1 knockout mice are small and exhibit behavioral abnormalities. Specific hypoplasias of retinal and mammary tissues suggest an unusual dependence on cyclin D1 function for tissue growth in those organs. The odd coincidences that cyclin D1 functions as the retinoblastoma gene kinase, together with associations between increased cyclin D1 expression and breast cancer, suggest, but do not prove, a special function of cyclin D1 in those tissues.

Taylor, Stephen J.; Shalloway, David

doi: 10.1002/bies.950180105pmid: 8593169

The finely tuned mechanisms that control cell cycle progression go awry in cancer, pointing to proto‐oncogene products as important players in cell‐cycle regulation. One such proto‐oncoprotein, c‐Src, has previously been directly implicated, based on its requirement for growth factor‐stimulated DNA synthesis. Roche et al.(1) have now shown that c‐Src or its close relatives are also required for cell division to occur. The demonstration of essential functions for the Src family at multiple points in the cell cycle raises important questions about the normal and transforming activities of these and other proto‐oncoproteins.

Staugaitis, Susan M.; Colman, David R.; Pedraza, Liliana

doi: 10.1002/bies.950180106pmid: 8593159

The myelin basic proteins are a set of peripheral membrane polypeptides which play an essential role in myelination. Their most well‐documented property is the unique ability to ‘seal’ the cytoplasmic aspects of the myelin membrane, but this is probably not the only function for these highly charged molecules. Despite extensive homology, the individual myelin basic proteins (MBPs) exhibit different expression patterns and biochemical properties, and so it is now believed that the various isoforms are not functionally equivalent in myelinating cells. We now think that while the major MBPs are intracellular adhesion molecules, some of the quantitatively less abundant isoforms that are expressed very early in development may have regulatory effects on the myelination program.

Pieau, Claude

doi: 10.1002/bies.950180107pmid: N/A

In many species of reptiles, sex is determined at fertilization by zygotic sex chromosome composition. In other species, including all crocodilians, most turtles and some lizards, sex is determined by temperature during the earlier stages of gonadal differentiation. The effects of exogenous estrogens, antiestrogens and aromatase inhibitors at different temperatures have unambiguously demonstrated the involvement of estrogens in sexual differentiation of the gonads. Aromatase is the enzyme that converts androgens to estrogens. Gonadal aromatase activity is well correlated with gonadal structure. It increases exponentially in differentiating ovaries, whereas it remains low in differentiating testes. Moreover, there is a high correlation between the thermosensitive periods for both ovary differentiation and increase in aromatase activity. We suggest that a thermosensitive factor intervenes, directly or indirectly, in the transcriptional regulation of the aromatase gene in reptiles with temperature‐dependent sex determination.

Schaller, Andreas; Ryan, Clarence A.

doi: 10.1002/bies.950180108pmid: 8593160

Insect and pathogen attacks activate plant defense genes within minutes in nearby cells, and within hours in leaves far distant from the sites of the predator attacks. A search for signal molecules involved in both the localized and distal signalling has resulted in the identification of an 18‐amino‐acid polypeptide, called systemin, that activates defense genes in leaves of tomato plants when supplied at levels as low as fmols/plant. Several lines of evidence support a role for systemin as a wound hormone. As with animal polypeptide hormones, systemin is derived from a larger precursor protein, called prosystemin, by limited proteolysis. Systemin has been shown by autoradiography to be phloemmobile and, by antisense technology, to be an essential component of the wound‐inducible, systemic signal transduction system leading to the transcriptional activation of the defensive genes. A search for the receptor of systemin has led to the identification in plant plasma membranes of a systeminbinding protein. However, this protein has properties not of a receptor, but of a furin‐like proteinase that cleaves systemin into smaller polypeptides. Systemin and its precursor prosystemin provide prototypes for the emerging possibilities that polypeptide hormones may have broad roles in signalling environmental stress responses, and in regulating plant growth and development as well.

Shaw, Gerry

doi: 10.1002/bies.950180109pmid: 8593162

Pleckstrin homology (PH) domains are a family of compact protein modules defined by sequences of roughly 100 amino acids. These domains are common in vertebrate, Drosophila, C. elegans and yeast proteins, suggesting an early origin and fundamental importance to eukaryotic biology. Many enzymes which have important regulatory functions contain PH domains, and mutant forms of several such proteins are implicated in oncogenesis and developmental disorders. Numerous recent studies show that PH domains bind various proteins and inositolphosphates. Here I discuss PH domains in detail and conclude that they form a versatile family of membrane binding and protein localization modules.

Lehmann, Michael

doi: 10.1002/bies.950180110pmid: 8593163

The up‐ and down‐regulation of the salivary gland secretion protein (Sgs) genes during the third larval instar of Drosophila melanogaster are controlled by fluctuations of the titre of the steroid hormone 20‐hydroxyecdysone (20E). Induction of these genes by a low hormone titre is a secondary response to 20E mediated by products of 20E‐induced ‘early’ genes. Surprisingly, in the case of the Sgs‐4 gene this response also requires a direct contribution of the 20E‐receptor complex. A model is presented which proposes that the Sgs genes, and other 20E‐regulated genes with similar temporal expression profiles, are regulated by complex hormone response units. The hormonal signal is effectively transmitted by these response units only after binding of additional factors, e.g. secretion enhancer binding proteins, which act together in a synergistic manner with the 20E receptor and early gene products to establish a stage‐ and tissuespecific expression pattern.