The Structure and Biology of T Cell Receptor Complex TCR/CD3

Summary: TCR/CD3 is a complex of eight subunits, which initiates biochemical events in T cell after antigen stimulation leading to T cell activation. The effector functions of T lymphocytes results from their specific structure including two functionally opposed regions: the polymorphic region specialized in specific antigen recognition (T cell receptor  �  TCR), and the signal transducing region (CD3 complex). All subunits of CD3 complex are involved in T cell activation, assembly of TCR/CD3 complex and its transport to the cell membrane. The special role of z-z homodimer results from the presence of three ITAM motifs in cytoplasmic domain of each z chain, what significantly amplifies the signal transduction in T cell, and additionally ?-? inhibits the signal leading to internalization of TCR/CD3 complex. In this article we reviewed the present knowledge of the structure of TCR/CD3 complex, the role of individual TCR/CD3 subunits in assembly events of octameric TCR/CD3 complex and intracellular transport of TCR/CD3 complex, including its transport to the cell membrane and its internalization after T cell activation.

Key words: T cell, TCR/CD3 complex, signal transduction, ITAM motif, di-leucine motif, internalization.

Triiodothyronine and Its Nuclear Receptors in Tumorigenesis

Summary: According to the generally accepted rules, gene and its protein product are thought to be involved in tumorigenesis when chromosomal anomalies and/or mutations of this gene as well as markedly disturbed expression and function of the encoded protein are found in tumor tissue. It seems that triiodothyronine receptors (TRs), belong to the group of such proteins. This hypothesis is supported by four facts. Firstly, physiological function of triiodothyronine (T3), exerted through TRs, is the regulation of proliferation, differentiation and apoptosis, the processes that are deeply disturbed in tumor tissue. Secondly, action of TRs is connected to the action of some protooncogenes (c-Jun, Mdm2) and tumor suppressors (p53). Thirdly, loss of heterozygosity (LOH) of chromosome fragments containing between others TR allele as well as disturbed expression of TR on the mRNA and protein level are observed in tumor tissues. Fourthly, TRa is a cellular homolog of v-erbA, a viral oncogene that behaves as a dominant negative mutant receptor. In addition, TR gene point mutations changing amino acid sequence are observed, resulting in abnormal receptor function as transcription activator. It was shown that mutants cloned from liver cancer behave as dominant negative mutants. It seems that in liver cancer and in papillary thyroid cancer, abnormal TR function may contribute to the process of tumorigenesis.

Key words: TH, thyroid hormone; T3, triiodothyronine; TR, nuclear thyroid hormone receptor; tumorigenesis; LOH, loss of heterozygosity; TR expression; TR mutations; dominant negative TR mutant.  

Molecular Cytogenetics in Establishment of Species-specific Traits and Their Variability in Analysis of Relationships in Angiosperms

Summary: Repetitive sequences, including retroelements, are the main genome component in angiosperm plants. Variations in their content both in the same species and within the genus, cause changes in the genome size. Each kind of repetitive sequences can be either species- and genome-specific or it can be present within the genus or families and display a characteristic localisation in chromosomes. Chromosome banding pattern, location of 18S-5.8, S-25S rDNA and 5S rDNA are considered to be species-specific. Among allopoliploids, as compared to ancestral genomes, changes consisting in translocations of chromosome fragments and translocations of repetitive sequences specific for one of the genome to another one, as well as reduction in the number of rDNA loci and their expression can occur. In establishing relationships among species the results of GISH method are important. 

Key words: molecular cytogenetics, karyotype, FISH, GISH, repetitive sequences, retroelements, species-specific traits

Mammalian Stem Cells: Presumed Source of Differentiated Cells for Transplantation

Summary: Human embryonic stem cells have been derived from inner cell masses of blastocysts and from few-week-old fetuses. They have been confirmed to persist in vitro in undifferentiated state for more than one year. It has been also proved that these cells differentiate in vivo � after transfer to recipient mice � and in vitro, into tissues originating from all three germ layers. The hopes have been raised that due to their properties human embryonic stem cells can be used for therapeutic purposes. Studies on mouse embryonic stem cells have confirmed  that it is possible to obtain differentiated, functional cells (e.g. neurons, oligodendrocytes) from them, which integrate with the proper tissue upon transfer to recipients. Interest in embryonic stem cells soon expanded to stem cells from adult tissues. Methods of isolation or enrichment of stem cells have been developed. In case of blood stem cells, muscle stem cells, and also stem cells of mesenchymal tissue, neural tissue and spermatogonia, their presence in the proper tissue have been proved after transfer to recipients. Stem cells from some tissues are able to transdifferentiate in vivo: in the  recipients they can be found in tissues other than their tissue of origin. For example, neural stem cells formed blood cells, muscle cells, gut epidermal cells and hepatocytes.

Key words: embryonic stem cells, stem cells from adult tissues

The Role of Telomeres and Telomerase in Tumor Progression.Diagnostic and Therapeutic Perspectives.

Summary: In a relatively short term the problem of chromosome replication has focused a wide attention within oncologists. The ends of chromosomes are capped by a hexanucleotide repeat sequences of nucleotides, refferred to as telomeres. Due to the polarity of conventional DNA synthesis, a loss of telomeric sequences occurs at each cell division. This telomeric erosion is frequently compared to a mitotic clock that elicits a signal for the onset of cellular senescence. Tumor cells have acquired the capacity to proliferate beyond the senescence checkpoint. This article describes the mechanisms responsible for telomere replication that enables indefinite proliferation of tumor cells and discussess the potential use of telomerase in diagnosis and treatment.

Key words: telomeres, telomerase, tumors
 

Inhibition of Posttranslational RAS Modification as a New Method of Cancer Treatment

Summary: RAS proteins play pivotal role in the control of cell growth and differentiation due to their ability to activate several downstream effectors. Mutations of Ras genes, occurring in approximately 30% of human cancers, result in a production of RAS proteins that continue to provide uncontrolled proliferative signals. The observation, that addition of a farnesyl moiety in a reaction catalyzed by farnesyltransferase is essential for the RAS proteins cell membrane association and their activity, has led to the development of farnesyltransferase inhibitors. This review aims to outline the role of RAS proteins in the signal transduction, their posttranslational modification and the ways in which deregulated RAS function may be involved in cancerogenesis. Subsequently, different types of farnesyltransferase inhibitors and their effectiveness in biological studies are rewieved.

Key words: RAS proteins, farnesyltransferase, farnesyltransferase inhibitors
 

Gap-Junctions and It`s Role in Apoptosis and Carcinogenesis

Summary: Gap junctions in multicellular organisms are indispensable in the process of holding homeostatic control of growth and differentiation of the cells. Such ways of delivering information among cells staying in strict contact are necessary for normal working of all organism. Loss of gap junction communication disturbs homeostasis of these cells. Cancer cells are characterized by disorders of growth and/or differentiation. Apoptosis is genetically determined death of cells, which homeostasis became irreversibly disturbed. In this study we try to explain the participation of gap junctions communication in cancerogenesis and in apoptosis.

Key words: Gap junctions, connexins, apoptosis, cancerogenesis