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Towards RNA export machinery
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Crosstalk between integrins and cadherins HODIVALA, K. I. and WA'i-I', F. M. (I 994) Evidence that cadherins play a role in the downregulation of integrin expression that occurs during keratinocyte terminal differentiation J. Cell Biol. 124, 589-600 The differentiation of epidermal keratinocytes is associated with their movement from a proliferating basal layer of the epidermis through multiple keratinocyte cell layers to the cell surface. During differentiation, their adhesive properties change. For example, integrins are restricted mostly to the proliferating basal layer and are downregulated as the cells differentiate, contributing to their expulsion from the basal layer. Of the cadherins, P-cadherin is mostly restricted to the basal layers of keratinocytes, whereas E-cadherin is found throughout the epidermis. Hodivala and Watt have studied the interplay between integrins and cad. herins during keratinocyte differentiation in vitro, by manipulating Caz+ levels in the culture medium. In a I,w. Caz' medium, cadherln.mediated cell.cell contacts and stratification were disrupted, but cells underwent terminal differentiation while attached to the culture substrate. Under these conditions, integrlns were not downregulated. However, when the Caz+ concentration was restored, cadherins redistributed to cell-cell contacts, and integrin protein and RNA levels were decreased. The downregulation of integrins was prevented at normal Caz+ levels by a combination of antibodies against E- and P-cadherin. Together, the results indicate that cadherins play a role in the down. regulation of integrins during the terminal differentiation of kera'~.inocytes. As one possible mechanism for the downregulation of integrins by cadherins, the authors suggest that both classes of adhesive receptor compete for a common cytoskeletal component needed for their stable expression. It will be interesting to determine whether cadherin levels can affect integrin expression in other develop. mental systems, and also whether downregulation of cadherins can trigger increased integrin levels.
p34 cc2 and apoptosis SHI, L, NISHIOKA, W. K., TH'NG, I., BRADBURY,E. M., LITCHFIELD, D. W. and GREENBERG,A. H. (1994) Premature p34 cdczactivation required for apoptosis Science 263, 1143-1145 Apoptosis can be considered as a defective cell cycle resulting in cell death instead of cell division. Indeed, there are striking similarities between the nuclear events taking place at the onset of mitosis and those seen in apoptosis, namely breakdown of the nuclear membrane and chromatin condensation. To investigate the possible role of the mitotic kinase p34 cd~ in apoptosis, the authors treated lymphocytes with fragmentin-2 (a serine protease) in the presence of perforin, thus mimicking the trigger in apoptosis induced by cytotoxic T lymphocytes. This treatment resulted in rapid and specific stimulation of p34 cd~ kinase activity, as evident from both the phosphorylation of peptide substrates by p34 cdc2 and the disappearance of tyrosine phosphorylation of p34 cdc2, Activation was dependent on the amount of protease used and coincided with DNA fragmentation in target cells. Inhibiting p34 cdc2with an excess of peptide substrate or the use of a temperature-sensitive p34 cdc2 mutant blocked DNA fragmentation. This study clearly indicates a causal relationship between inappropriate activation of p34 cdc2and apoptosis. Activation of the kinase was necessary for apoptosis stimulated by fragmentin-2 as well as by staurosporin, a protein kinase inhibitor that activates a bcl-2-regulated apoptosis pathway; it may thus represent a crucial common step at which independent apoptotic pathways converge.
Towards RNA export machinery ]ARMOLOWSKI, A., BOELENS,W. C., IZAURRALDE,E. and MATrAJ, I. W. (1994) Nuclear export of different classes of RNA is mediated by specific factors J. Cell Biol. 124, 627-635 Export of RNA molecules from the nucleus is a major component of nucleo. cytoplasmic traffic, but very little is known about the mechanisms involved. It is temperature dependent and saturable, implying that it is mediated by proteins. In this paper, the authors have investigated whether separate export mechanisms exist for different types of RNA or whether all RNA types interact with a common transport machinery. Export was assayed by injection of radiolabelled RNA species into the nuclei of Xenopus oocytes and then, after incubation, separation of the nuclei and cytoplasm to look at the RNA distribution. The labelled RNAs were injected either alone or with varying amounts of unlabelled competitor RNA, of the same or different type. The overall finding is that export of tRNA, mRNA and snRNA can be efficiently competed by RNA of the same type, but not by different ones. Cross-competition was observed at high concentrations of competitor, as has been reported previously, and also with certain types of ribonucleotide homopolymers. Thus, the limiting component in export appears to vary for different types of RNA, but interactions with common export components are also involved. The most likely scenario is that initial steps in export involve RNA species-specific fac. tors and that the pathways then converge at or before the nuclear pore complex where transport occurs.
TRENDS IN CELLBIOLOGYVOL. 4 JUNE 1994
201
Crosstalk between integrins and cadherins HODIVALA, K. I. and WA'i-I', F. M. (I 994) Evidence that cadherins play a role in the downregulation of integrin expression that occurs during keratinocyte terminal differentiation J. Cell Biol. 124, 589-600 The differentiation of epidermal keratinocytes is associated with their movement from a proliferating basal layer of the epidermis through multiple keratinocyte cell layers to the cell surface. During differentiation, their adhesive properties change. For example, integrins are restricted mostly to the proliferating basal layer and are downregulated as the cells differentiate, contributing to their expulsion from the basal layer. Of the cadherins, P-cadherin is mostly restricted to the basal layers of keratinocytes, whereas E-cadherin is found throughout the epidermis. Hodivala and Watt have studied the interplay between integrins and cad. herins during keratinocyte differentiation in vitro, by manipulating Caz+ levels in the culture medium. In a I,w. Caz' medium, cadherln.mediated cell.cell contacts and stratification were disrupted, but cells underwent terminal differentiation while attached to the culture substrate. Under these conditions, integrlns were not downregulated. However, when the Caz+ concentration was restored, cadherins redistributed to cell-cell contacts, and integrin protein and RNA levels were decreased. The downregulation of integrins was prevented at normal Caz+ levels by a combination of antibodies against E- and P-cadherin. Together, the results indicate that cadherins play a role in the down. regulation of integrins during the terminal differentiation of kera'~.inocytes. As one possible mechanism for the downregulation of integrins by cadherins, the authors suggest that both classes of adhesive receptor compete for a common cytoskeletal component needed for their stable expression. It will be interesting to determine whether cadherin levels can affect integrin expression in other develop. mental systems, and also whether downregulation of cadherins can trigger increased integrin levels.
p34 cc2 and apoptosis SHI, L, NISHIOKA, W. K., TH'NG, I., BRADBURY,E. M., LITCHFIELD, D. W. and GREENBERG,A. H. (1994) Premature p34 cdczactivation required for apoptosis Science 263, 1143-1145 Apoptosis can be considered as a defective cell cycle resulting in cell death instead of cell division. Indeed, there are striking similarities between the nuclear events taking place at the onset of mitosis and those seen in apoptosis, namely breakdown of the nuclear membrane and chromatin condensation. To investigate the possible role of the mitotic kinase p34 cd~ in apoptosis, the authors treated lymphocytes with fragmentin-2 (a serine protease) in the presence of perforin, thus mimicking the trigger in apoptosis induced by cytotoxic T lymphocytes. This treatment resulted in rapid and specific stimulation of p34 cd~ kinase activity, as evident from both the phosphorylation of peptide substrates by p34 cdc2 and the disappearance of tyrosine phosphorylation of p34 cdc2, Activation was dependent on the amount of protease used and coincided with DNA fragmentation in target cells. Inhibiting p34 cdc2with an excess of peptide substrate or the use of a temperature-sensitive p34 cdc2 mutant blocked DNA fragmentation. This study clearly indicates a causal relationship between inappropriate activation of p34 cdc2and apoptosis. Activation of the kinase was necessary for apoptosis stimulated by fragmentin-2 as well as by staurosporin, a protein kinase inhibitor that activates a bcl-2-regulated apoptosis pathway; it may thus represent a crucial common step at which independent apoptotic pathways converge.
Towards RNA export machinery ]ARMOLOWSKI, A., BOELENS,W. C., IZAURRALDE,E. and MATrAJ, I. W. (1994) Nuclear export of different classes of RNA is mediated by specific factors J. Cell Biol. 124, 627-635 Export of RNA molecules from the nucleus is a major component of nucleo. cytoplasmic traffic, but very little is known about the mechanisms involved. It is temperature dependent and saturable, implying that it is mediated by proteins. In this paper, the authors have investigated whether separate export mechanisms exist for different types of RNA or whether all RNA types interact with a common transport machinery. Export was assayed by injection of radiolabelled RNA species into the nuclei of Xenopus oocytes and then, after incubation, separation of the nuclei and cytoplasm to look at the RNA distribution. The labelled RNAs were injected either alone or with varying amounts of unlabelled competitor RNA, of the same or different type. The overall finding is that export of tRNA, mRNA and snRNA can be efficiently competed by RNA of the same type, but not by different ones. Cross-competition was observed at high concentrations of competitor, as has been reported previously, and also with certain types of ribonucleotide homopolymers. Thus, the limiting component in export appears to vary for different types of RNA, but interactions with common export components are also involved. The most likely scenario is that initial steps in export involve RNA species-specific fac. tors and that the pathways then converge at or before the nuclear pore complex where transport occurs.
TRENDS IN CELLBIOLOGYVOL. 4 JUNE 1994
201