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Histone deacetylase inhibitors (HDIs) causes irreversible cell cycle arrest and senescence of E1A+Ras transformed cells. HDI sodium butyrate (NaB) affects the DNA repair and consequently modulates the phosphorylation of DNA breaks marker histone H2AX. For Gadd45 family proteins shown the role in regulation of cell proliferation, apoptosis and DNA repair. In the present paper, we studied the effect of NaB on the DNA repair through Gadd45a protein modulation. Our results indicate that suppression of Gadd45α reduces the DNA repair efficiency, in both basal, and NaB-dependent. However NaB-induced supression of DNA repair is reduced in Gadd45-expressing transformed cells. This is the result of Gadd45α accumulation in the nucleus and redistribution of oligomeric forms of Gadd45 under NaB treatment. This results in changing of Gadd45α interaction with proteins involved in the cell cycle progression and DNA repair regulation. NaB amplified the interaction of Gadd45 with p21/Waf1 protein, thereby reducing the amount of the p21/Waf1 in complex with PCNA. Thus, in the absence Gadd45α the amount of DNA breaks accumulates due to the reduced efficiency of repair, while HDIs dependent induction of Gadd45α promotes the DNA repair. DNA damages induced with HDIs or genotoxic agents could not be repaired under the lack of Gadd45α. As a result Gadd45 deficient transformed cells initiate apoptotic death program.

Ras genes were first identified in the 1960s as transforming oncogenes that caused tumors in rats infected with Harvey and Kirsten sarcoma viruses (Ha-ras and Ki-ras oncogenes, accordingly). Subsequently, transforming ras genes were found in human cancer cells. Further investigations of neuroblastoma cells resulted in the finding of the third ras gene in the human, which was called N-ras. Ras gene products play an important role in the processes of cellular proliferation and differentiation and are controlled by receptor tyrosine kinases. Using drosophila as a model object allowed us to perform a successful genetic analysis while studying the functions of ras genes. Three polytene chromosome bands were detected in D. melanogaster with the help of the v-Ha ras sampling. According to Bridges' map, all three bands (Dras1, Dras2, Dras3) were mapped to regions 85D, 64B, and 62B of chromosome 3. Among them, only Drasl has a common origin with ras genes of mammals. Although there are numerous investigations of the role played by ras genes in the de- velopment of insects, this problem is still not fully understood. The importance of ras gene variations in the course of the evolutionary process has been insufficiently studied as well. Currently, Ras target proteins are actively identified, their signal pathways, as well as effects of influencing these pathways in the drosophila tissues, are studied in the cells of yeast and mammals. The main functions of Ras protein is in the signaling pathways controlling mutations during drosophila's morphogenesis and the connections of ras gene with phenotypic symptoms of tumors.

The efficacy of cycloferon use in the treatment of frequently ill children (FIC) was estimated by the dynamics of the blood plasma proteomic profile. A group of FIC at the age of 4 to 10 years were observed. Cycloferon was administered according to the standard schemes. The results were analysed by the computer programme complex, including the anamnesis, clinical symptoms, infection index, findings of the electrophoretic and mass-spectrometric analyses of the blood plasma before and after the drug use. The intensity indices of the Rho and Ras proteins, the signal pathways, in the blood proteomic profile proved to be sensitive and specific parameters for estimating the regimens of the therapy and prophylaxis of respiratory tract infection in FIC. The epidemiologic efficacy of cycloferon, as an agent of nonspecific immunoprophylaxis for FIC during seasonal prevalence of respiratory tract infection and influenza cases was shown.

The review considers mechanisms of Ca2+-dependent regulation of cell growth, differentiation, and apoptosis in cells of the higher eukaryotes by modulation of the signal Ras-MAPK pathway.

Theoretical conformational analysis was used to study the spatial structure of a putative binding site responsible for binding of p21 oncoproteins to other oncoproteins. Conformational properties of the isolated address sequence localized in fragment 34-46 of native p21 and of the decapeptide molecule corresponding to the 35-44 sequence in the primary structure of oncoproteins of this family were revealed. Our calculations demonstrated a similarity between the spatial structures of the peptides, which confirms the hypothesis on the identity of their biological functions.

Seven haploid strains (four with the MAT alpha mating type and three with the MATa mating type) were selected from the Peterhof genetic collection of yeast. Previous phenotypic analysis assigned six of these strains to a physiological group of strains with a lower activity of the Ras/cAMP signal transduction pathway. The haploids were crossed, and the resulting 12 diploids showed higher glycogen accumulation, tolerance to heat shock and nitrogen starvation, and sporulation in complete media. Ten of the diploids expressed the hypersporulation phenotype (higher sporulation efficiency). The phenotypic characters of these ten diploids suggested a reduced activity of the Ras/cAMP pathway. All 12 diploids were tested for sporulation and production of two groups of asci (those with one or two spores and those with three or four spores) as dependent on culture conditions (21, 30, or 34 degrees C; standard sporulation medium or a complete medium containing potassium acetate or glycerol in place of glucose). Sporulation proved to depend on temperature and medium composition. The results are collated with the data on yeast phenotypes associated with a lower activity of the Ras/cAMP signal transduction pathway.

A study was made of the effect of activated oncogene N-RAS on the function of tumor suppressor p53 and the proliferating ability of rat embryo fibroblasts REF52. The proliferation rate and the portion of S-phase cells increased in the first three days of N-RAS expression. After 5-7 days, the p53 function was enhanced, as manifest in increased p53 lifespan and nuclear content and induced transcription of p53-responsive genes. In particular, Cdk2 p21WAF1/CIP1, an inhibitor of cyclin-dependent kinase 2, was produced to a higher level and arrested the cell cycle in G1. Cells with abrogated or dramatically inhibited N-RAS expression were generated at this stage. Having a selective advantage, these cells gradually displaced N-RAS-expressing cells arrested in G1, so that one month after oncogene induction the culture mostly consisted of morphologically normal, actively proliferating Res-negative cells. Neither cell cycle arrest nor reversion to the normal phenotype were observed in N-RAS expressing cells devoid of the p53 function. Thus, p53 prevented stable N-RAS-induced transformation of REF52 cells, arresting the cell cycle and expediting revertant selection.

Recent achievement of molecular biology and neurophysiology resulting in remarkable progress in the understanding of processes of neurodifferentiation, playing the relevant role both in an ontogenesis and working of adult brain. New representations have been formed about a role of cytoskeletal proteins in mechanisms of neurites growth. In the review we discussed recent data regarding mechanisms of neuronal differentiation regulation. The special interest is given to a problem of influence of electrical fields on neuronal growth and differentiation. The mechanisms of signal transduction from a cell surface to nuclear are in detail analyzed. The classification of the physical and chemical factors of growth neurites regulation is given.