Advances in Cell biology, vol. 32, 2005, issue 1

Summary: Melanoma is one of the most aggressive human cancers. Its cells are inevitably resistant to conventional therapies. In recent years, better understanding of melanoma biology, has led to the development of a number of new potential therapeutic agents. Many of these compounds are being tested in early phase of clinical trials, some have already reach phase III. In August 2011 the FDA approved a new drug - Wemurafenib (PLX4032) to treatment unresectable and/or metastatic melanoma. The current article is an overview of the major proteins, signaling pathways and networks involved in the development and progression of melanoma, with particular emphasis on elements that are the most promising targets for anticancer therapy.

Key words: melanoma, targeted therapy

Summary: Summary: Gibberellins (GAs), as one of the most important phytohormones, control different aspect of plant growth and development including seed germination, stem elongation and flower induction. Among more than a hundred and thirty GAs identified from plants, fungi and bacteria only a small number of them, such as GA₁, GA₃, GA₄, GA₅, GA₆ and GA₇, are thought to function as bioactive hormones. Therefore, many non-bioactive GAs exist in plants as precursors or deactivated metabolites. Recent biochemical, genetic and molecular studies have elucidated in detail the mechanism of GA perception and signal transduction in plants (fig. 11). In the first step the GA signal is perceived by the GA receptor – GID1 (GA insensitive dwarf 1), which is a soluble protein that is localized to both cytoplasm and nucleus. There is a single GID1 gene in rice (Oryza sativa), but three ortholoques in Arabidopsis thaliana (GID1a, GID1b, GID1c) with overlapping functions. The binding of bioactive GAs to GID1 promotes an interaction between GID1 and the DELLA-domain of DELLA proteins, which are main repressors of gibberellin pathway. The DELLA motif is essential for this interaction, because its deletion results in an inability to interact with GID1, despite the presence of GAs. Whereas rice has only one DELLA protein – SLR1 (slender rice 1), the Arabidopsis genome encodes five DELLAs – GAI (GA insensitive), RGA (repressor of GA1-3), RGL1, RGL2 and RGL3 (rga like 1/2/3). Structurally, DELLAs are a subgroup of proteins that belong to the GRAS (gai, rga, scarecrow) family of transcriptional regulators. The binding of DELLA by GA-GID1 enhances the affinity between DELLA and a specific SCF E3 ubiquitin-ligase complex involving the F-box proteins AtSLY1 and OsGID2 in Arabidopsis and rice, respectively. In turn, SCF^SLY1/GID2 promotes the ubiquitinylation and subsequent destruction of DELLAs by the 26S proteasome. This situation is a key event in GA signaling and affect on transcription factors which regulate activity of target genes. The mechanism of hormonal signal transduction, presented in this paper has been described only in plants, however it can supposed, that this novel mechanism may also exist in other organisms.

Summary: Strigolactones, are the new regulators of plant growth and development. The first information about strigolactones came from experiments verifying the interactions between host plants and parasites of the Orobanchaceae family. In these interactions some substances from root exudates play critical role in the induction of parasitic plants seed germination. Isolation and identification of new representatives of these substances revealed their similar chemical structure containing the lactone group. These compounds have been termed to as strigolactones after the name of the parasite Striga sp. and lactone group. The next step in the research carried out on strigolactones was to prove that these regulators act as branching factors for symbiotic arbuscular mycorrhizal fungi (AMF). This fact may explain why plants exude strigolactones that enable them to be located by their enemies. The parasitic plants that evolved later than AMF may then have developed a detection system for strigolactones as cues to find living host roots in their vicinity. The new function of strigolactones is their role in inhibiting shoot branching (discovered in 2008). Analysis of several mutants with increased shoot branching, in which known hormones were not responsible for the bud outgrow, showed that strigolacones play critical role in negatively regulated branching in plants. Strigolactone mutants found in Arabidopsis, pea, rice and tomato always had a similar phenotype – these plants were smaller and more-bushy than parental varieties. The new functions of strigolactones (e.g. regulation of mesocotyl elongation or control of the root growth and root hair growth) are described. Analysis of mutants with bushy-like phenotypes enabled the identification of the first genes involved in strigolactone biosynthesis and signaling. The studies of molecular basis of these processes are necessary to understand the mechanisms by which strigolactones regulate plant growth and development and to describe the strigolactone interactions with fitohormones. It was proved that strigolactones control the level of auxin and together with this hormone negatively regulate shoot branching. Moreover, the first step of strigolactones biosynthesis is similar to one of the steps of abscisic acid biosynthesis. The main genes involved in strigolactone biosynthesis – CCD7 and CCD8 – were identified in chloroplasts, together with genes responsible for the control of this process – IAA12 and IGI1. The first inhibitor of strigolactone synthesis – TIS13 – was also described. Analyses carried out on rice mutants insensitive to synthetic analog of strigolactone reveled proteins that may play a role as strigolactones receptors - FC1, D3 and D14. It is interesting that the amino acid sequence and/or conformation of these proteins are similar to different proteins identified as receptors for fitohormones, such as auxin, jasmonates or gibberellins. Experiments on different species, such as Arabidopsis, pea, rice or tomato, showed that the mechanisms of strigolactone biosynthesis and signaling are conserved in plants. The paper presents a review of the history about strigolactones discovery, molecular basis of RMS/MAX/D pathway and their functions in plants.

Key words: parasites, regulators of plant growth and development, RMS/MAX/D pathway, shoot branching, strig

Summary: Central nervous system is in unique manner isolated from the direct influence of external environment. This isolation is possible thanks to the existence of complicated in its structure, blood-brain barrier, which is a compilation of anatomical as well as physiological attributes. It is characteristic that connections between endothelial cells are tightening, which is an obvious passive transport obstacle and active carriage through the barrier dominates. Disruption of barrier continuity can happen due to many neurological diseases, but undoubtedly, the main reasons are brain injuries, which may increasingly be growing medical problem. Therefore, so important are every type of studies on structure and permeability of blood-brain barrier because they provide more and more detailed data, which broaden our knowledge.

Summary: Apart from epigenetics associated with environmental and behavioral factors, genetic variants contribute to human variation and may cause either disorders or neutral polymorphisms, such as single nucleotide polymorphisms and copy number variants. Genome rearrangements include different regions of DNA, from single base pair to chromosomal regions of millions of nucleotides. There are four main mechanisms of genetic variants origin: non-allelic homologous recombination, non-homologous end-joining, fork stalling and template switching and microhomology mediated break induced replication. mRNA retrotransposition may also lead to some genome rearrangements. Molecular diagnostic is currently based on automated techniques that identify DNA variants and predict treatment response dependent on genetic factor. Knowledge in the field of genetic variants contributes to molecular diagnostics that improve life conditions of patients.

Keywords: genetic variants, polymorphisms, recombination, molecular diagnostic