Cellular Regulatory Systems. Mechanisms of Feedback Loops and Substrate-Product Dependency in the Cell Cycle

Summary: Temporal ordering of events in the cell cycle is directed by a highly sophisticated control system. Their checkpoints are signal-transduction pathways specific for either abnormally or incompletely assembled cellular structures. Since the main role of all these checkpoints is to make a decision, whether or not the cell division cycle has to be continued, particular elements of these control mechanisms deserve special attention as promising targets for pharmacological treatment of cancer. Signaling pathways are interconnected and form a complex network that carries information from the outside to the inside of the cell and, then, execute biochemical or physiological responses. Here we review recent advances in our understanding of the higher-order biological functions of (1) the natural, well-known signaling system responsible for the cdc25-mediated activation of mitosis, and (2) the basic properties of the cell cycle checkpoints. Initiation of mitosis has been shown to exhibit bistable responses, while cell cycle checkpoints have been shown to function as an oscillator with positive, double-negative feedback loops and substrate-product dependencies.

Key words: cell cycle, cell cycle checkpoints, feedback loops, substrate-product dependency.  

Triple-Stranded DNA and its Applications

Summary: Triple-stranded DNA structures can be formed as a result of sequence-specific interactions between double-stranded DNA and single-stranded oligonucleotides called TFOs (triplex forming oligonucleotides). There are many potential uses of DNA triplexes induced by TFOs. They may interfere with transcription and replication. They may also induce mutations and homologous recombination, being a potential tool in gene therapy. There is a need of further research to develop a strategy of using TFOs.

Key words: triple-stranded DNA, triplex forming oligonucleotides, peptide nucleic acids.  

ALCAM/CD166 (Activated Leukocyte Cell Adhesion Molecule) – Adhesion Molecule Affecting Growth, Development, Aggregation and Migration of Normal and Neoplastic Cells

Summary: Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) belongs to an immunoglobulin superfamily and is also a member of small subgroup of transmembrane proteins. The mature proteins from this group are determined by presence of three structural fragments: extracellular, transmembrane and short cytoplasmic region. ALCAM/CD166 mediates heterophilic (ALCAM/CD166-CD6) and homophilic (ALCAM/CD166- ALCAM/CD166) cells adhesion in wide variety, both tissue and cultured cell lines. ALCAM/CD166 participation in hematopoesis process, nerve developing and immune response was described. ALCAM/CD166 plays also important role in cancer development. Early increase of this adhesion molecule expression and later loss the ALCAM/CD166 mediated cells contact in tumour progression e.g. prostate cancer, malignant melanoma or breast cancer was noticed. The latest research and hypothesis describing ALCAM/CD166 involving in normal and neoplastic cells adhesion, growth and developing are recapitulated in this review.

Key words: ALCAM/CD166, cells adhesion, cancers, metastasis, MMP2.  

Tail Bud in Development of Vertebrate Embryos

Summary: After gastrulation the caudal part of vertebrate embryo, designated tail bud, forms a mass of undifferentiated mezenchymal cells, from which the lumbosacral and caudal parts of the body develop. The mesenchymal cells have the potential to give rise to a variety of different tissues including the posterior or "secondary" neural tube, tail gut, and somites and their derivatives. Some molecular mechanisms involved in the tail bud differentiation were described and the role of tail bud as organiser of caudal part of the veterbrate body is discussed.

Key words:  tail bud, caudal organizer, secondary neurulation, somitogenesis.  

The Role of Cellular Membrane Transport in the Multidrug Resistance

Summary: Multidrug resistance is a frequent cause of the failure of chemotherapy in the treatment of cancer. Many cellular mechanisms, by which tumor cells may evade the cytotoxic effects of anticancer agents, were investigated. Multidrug resistance strongly linked to the overexpression of membrane-associated glycoprotein is one of the best understood and most intensively studied forms of mammalian drug resistance. Some of the membrane protein responsible for drug efflux has been identified and its structure and function characterized. They appear to play an important role in drug efflux. Expression of these proteins in many human tumors, as well as in normal tissues has been shown. A large number of drugs, which inhibit the function of transported protein, have been identified. Many of them have proven toxic effects, and thus the identification of novel agents for potential clinical use has taken on great importance.

Key words: multidrug resistance, P-glycoprotein, transport.  

The Function of Thiol Compounds in Plants in Heavy Metal Stress

Summary: A steady growth of heavy metal content being mainly the result of anthropogenic activity is observed in almost all soils. The presence of increased metal concentration leads to many unfavorable changes in plant cell functions. The presence of heavy metal ions in plant cells causes activation of the phytochelatin detoxication system, which consists of cysteine, glutathione and its homologs – phytochelatins – and also enzymes of glutathione biosynthesis g-glutamylcysteine synthetase, glutathione synthetase and phytochelatin synthase – an enzyme responsible for the synthesis of PCs. Ions of metals which have penetrated the cytoplasm are chelated by glutathione or short-chained PCs thus creating low-molecular complexes which are then transported into the vacuole. More stabile complexes with high sulfur content are formed in the vacuole. In the recent years growing attention has been paid to the possibility of using plants in removal or inactivation of contamination from the soil and surface water – this process is called phytoremediation.

Key words: heavy metals, detoxication, glutathione, phytochelatins, phytoremediation.
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Molecular Genetics of Nijmegen Breakage Syndrome

Summary: The chromosomal instability disorder, Nijmegen Breakage Syndrome (NBS, OMIM 251260) is a rare disease with perhaps 140 cases world-wide. They are mostly of eastern and central European origin, especially Polish – 81 cases. The clinical picture is characterized by microcephaly, growth retardation and immunodeficiency. High incidence of malignancies at early childhood is streaking hallmarks of NBS. Inheritance of NBS follows an autosomal recessive trait. The disease is caused by mutations in NBS1 gene. A truncating 5bp deletion (657del5) in exon 6 of the NBS1 gene has been identified in 90% of NBS patients. All known disease-causing mutations result in premature truncation of the nibrin – product of the NBS1 gene. Nibrin is a member of the MRE11/RAD50 protein complex involved in the repair of DNA double-strand breaks. Cells from NBS patients show chromosomal instability and cellular checkpoints defects as a marked sensitivity to ionizing irradiation and radiomimetic agents.

Key words:  chromosomal instability Nijmegen Breakage Syndrome, NBS1 gene, nibrin..  

Prolactin Receptors in Human and Various Animal Species

Summary: Membrane prolactin receptor differs among species and in the individual. Various izoforms of receptor expressed on tissues of that same individual enables regulation of signal transduction generated by prolactin. Following article describes available information presenting expression of various izoforms of prolactin receptor in human and other species and latest updates in intracellular processing, subsequent to ligand's binding initiating activation promoters of definite genes.

Keywords:  prolactin receptor, izoforms of prolactin receptor; signal transduction, cytokines.