Nucleolar control of p53: a cellular Achilles’ heel and a target for cancer therapy

Nucleoli perform a crucial cell function, ribosome biogenesis, and of critical relevance to the subject of this review, they are also extremely sensitive to cellular stresses, which can cause loss of function and/or associated structural disruption. In recent years, we have learned that cells take advantage of this stress sensitivity of nucleoli, using them as stress sensors. One major protein regulated by this role of nucleoli is the tumor suppressor p53, which is activated in response to diverse cellular injuries in order to exert its onco-protective effects. Here we discuss a model of nucleolar regulation of p53, which proposes that key steps in the promotion of p53 degradation by the ubiquitin ligase MDM2 occur in nucleoli, thus providing an explanation for the observed link between nucleolar disruption and p53 stability. We review current evidence for this compartmentalization in p53 homeostasis and highlight current limitations of the model. Interestingly, a number of current chemotherapeutic agents capable of inducing a p53 response are likely to do so by targeting nucleolar functions and these compounds may serve to inform further improved therapeutic targeting of nucleoli.     

Chemical composition of decomposing stumps in successive rotation of Chinese fir （Cunninghamia lanceolata （Lamb.） Hook.） plantations

Decomposition of stumps in successive rotation of Chinese fir （Cunninghamia lanceolata （Lamb.） Hook.） plantations was studied using a chronosequenee approach. The results showed that decomposition rate constant of Chinese fir stump was 0.02695 as calculated from Olson＇s model. The N content of stump increased during the first two-year decomposition. When the dead stump C/N ratio was 463.2 ± 27.3, the stumps started to release N. The pattern of P release was similar to that for N. However, K content of stumps showed a consistent declining trend over time during the whole decomposition. ^13C nuclear magnetic resonance spectroscopy with cross polarization and magic-angle spinning （^13C CPMAS-NMR） was used to analyse organic carbon （C） components in decomposing stumps. The ^13C CPMAS-NMR spectra of stumps displayed that stump was dominated by cellulose and hemieellulose. The spectra also showed the accumulation of intensity in alkyl C, aromatic C, and earboxyl C spectral regions, which was expected as the labile cellulose and hemieellulose components in O-alkyl C spectral region were selectively decomposed first.     

Structure and function of eukaryotic peptide transporters

The cotransport of protons and peptides is now recognised as a major route by which dietary nitrogen is absorbed from the intestine, and filtered protein reabsorbed in the kidney. Recently, molecular biology has had a very substantial impact on the study of peptide transport, and here we review the molecular and functional information available within the framework of physiology. To this end we consider not only the mammalian peptide transporters and their tissue distribution and regulation but also those from other species (including Caenorhabditis elegans) which make up the proton-dependent oligopeptide transport superfamily. In addition, understanding the binding requirements for transported substrates may allow future design and targeted tissue delivery of peptide and peptidomimetic drugs. Finally, we aim to highlight some of the less well understood areas of peptide transport, in the hope that it will stimulate further research into this challenging yet exciting topic.     

Importance of stirring in the development of an iron-fertilized phytoplankton bloom

The growth of populations is known to be influenced by dispersal, which has often been described as purely diffusive. In the open ocean, however, the tendrils and filaments of phytoplankton populations provide evidence for dispersal by stirring. Despite the apparent importance of horizontal stirring for plankton ecology, this process remains poorly characterized. Here we investigate the development of a discrete phytoplankton bloom, which was initiated by the iron fertilization of a patch of water (7 km in diameter) in the Southern Ocean. Satellite images show a striking, 150-km-long bloom near the experimental site, six weeks after the initial fertilization. We argue that the ribbon-like bloom was produced from the fertilized patch through stirring, growth and diffusion, and we derive an estimate of the stirring rate. In this case, stirring acts as an important control on bloom development, mixing phytoplankton and iron out of the patch, but also entraining silicate. This may have prevented the onset of silicate limitation, and so allowed the bloom to continue for as long as there was sufficient iron. Stirring in the ocean is likely to be variable, so blooms that are initially similar may develop very differently.     

Manipulating the activity of immobilized enzymes with different organo-smectite complexes

Summary Enzymes may be immobilized on hydrophobic surfaces of organo-smectite complexes. The immobilized enzyme may be active, partially active, or inactive depending on the nature of the organic surface. These materials may be useful as models for enzymes in natural systems, and in medicine and industry.This work was partially supported by the National Science Foundation under Grant No. CHE-8306583. Journal Article No. 11603 of the Michigan Agricultural Experiment Station.     

Mutations in a delta 8-delta 7 sterol isomerase in the tattered mouse and X-linked dominant chondrodysplasia punctata. jderry@immunex.com.

Tattered (Td) is an X-linked, semi-dominant mouse mutation associated with prenatal male lethality. Heterozygous females are small and at 4-5 days of age develop patches of hyperkeratotic skin where no hair grows, resulting in a striping of the coat in adults. Craniofacial anomalies and twisted toes have also been observed in some affected females. A potential second allele of Td has also been described. The phenotype of Td is similar to that seen in heterozygous females with human X-linked dominant chondrodysplasia punctata (CDPX2, alternatively known as X-linked dominant Conradi-Hünermann-Happle syndrome) as well as another X-linked, semi-dominant mouse mutation, bare patches (Bpa). The Bpa gene has recently been identified and encodes a protein with homology to 3beta-hydroxysteroid dehydrogenases that functions in one of the later steps of cholesterol biosynthesis. CDPX2 patients display skin defects including linear or whorled atrophic and pigmentary lesions, striated hyperkeratosis, coarse lusterless hair and alopecia, cataracts and skeletal abnormalities including short stature, rhizomelic shortening of the limbs, epiphyseal stippling and craniofacial defects (MIM 302960). We have now identified the defect in Td mice as a single amino acid substitution in the delta8-delta7 sterol isomerase emopamil binding protein (Ebp; encoded by Ebp in mouse) and identified alterations in human EBP in seven unrelated CDPX2 patients.     

Bovine pituitary intraglandular colloid fraction F5 localized in the rat endocrine pancreas

Bovine pituitary intraglandular colloid thought to be a waste product, is the holocrine secretion of intermediate lobe cells. It is housed in the intraglandular lumen (residual lumen) and is extruded into the venous circulation of the cavernous sinuses via clefts in the capsule of the gland aligned with the intraglandular lumen. Intraglandular colloid, fraction F5 (mol.wt 34,000), radiolabeled with (125I)Na and injected (0.15 ml) into the right internal jugular vein of male Wistar rats, accumulated in the endocrine pancreas. Autoradiographs showed that the material had specifically localized in the capillary network of the endocrine pancreas. Since the intermediate lobe is poorly vascularized, intraglandular colloid is considered to be the transport medium for intermediate lobe materials.     

The helical s constant for alanine in water derived from template-nucleated helices.

Formation of alpha helices from disordered polypeptides depends on the degree to which amino acids favour the helical state. The folding of helical oligopeptides can be modelled by two parameters: sigma which reflects helix initiation and s which reflects propagation of a pre-existing helix and measures helical bias. Scheraga has reported s values for oligopeptides of about 1.1, implying a weak helical bias for amino-acid residues. By contrast, certain helical peptides studied by Baldwin seem to require much larger s values for alanine. Resolution of this inconsistency requires experiments that disentangle the ease of propagation from that of initiation. In this study varying lengths of polyalanine are linked to a 'template' that initiates helical structure and permits study solely of propagation. We report here that the s value for alanine in water is close to 1, supporting the earlier results of Scheraga but not the more recent results of Baldwin.