The integrity of eukaryotic cellular function depends on molecular and biochemical compartmentalization. The transport of macromolecules between compartments requires specific and energydriven mechanisms. It occurs through a class of transport proteins known as karyopherins, which are divided in three different groups (exportins, importins, and transportins). The ubiquitous exportin Chromosome Region Maintenance 1 (CRM1) is involved in the transport of many proteins and RNA molecules from nucleus to cytoplasm. We have reviewed the available evidence supporting the relevance of CRM1 in the biology of several human neoplasms, its potential role in drug resistance, and its promise as a therapeutic target. Here we discuss different cancer related proteins (tumor suppressor genes, oncogenes, and enzymatic therapeutic targets), their function, and their association with CRM1, as well as agents that specifically inhibit CRM1, their mechanism of action, and their clinical relevance in certain human neoplasms. The directionality of nuclear transport and the specific molecular cargo in question are of paramount importance when examining the effects that CRM1 inhibition may have on cellular pathophysiology. The available data point out the potential role of CRM1-dependent nuclear export of regulatory proteins in the biology of certain human malignancies. Further studies should expand and clarify the importance of this mechanism in the pathobiology of human neoplasia.
Dexras1 and RHES, monomeric G proteins, are members of small GTPase family that are involved in modulation of pathophysiological processes. Dexras1 and RHES levels are modulated by hormones and Dexras1 expression undergoes circadian fluctuations. Both these GTPases are capable of modulating calcium ion channels which in turn can potentially modulate neurosecretion/hormonal release. These two GTPases have been reported to prevent the aberrant cell growth and induce apoptosis in cell lines. Present review focuses on role of these two monomeric GTPases and summarizes their role in pathophysiological processes.
Cell free DNA (cf-DNA) refers to all non -ncapsulated DNA present in the blood stream which may originate from apoptotic cells as a part of the physiological cell turnover, or from cancer cells or fetal cells. Recent studies have highlighted the utility of cfDNA analysis for genetic profiling of cancer, non-invasive prenatal testing besides many other clinical applications. In our review we discuss the sources of cfDNA in the body, the techniques most commonly being used for its isolation and analysis, the applications of cfDNA testing and the associated pros-cons. We conclude that for prenatal testing, cfDNA analysis provides an effective, non-invasive and safer alternative to traditional amniocentesis and chorionic villus sampling tests. Also, in cancer patients, cfDNA analysis is useful for genetic profiling and follow-up during treatment. However, standardization of methods of isolation and analysis has become crucial for the success of widespread use of cfDNA analysis.
Objective: Dexamethasone-induced Ras-related protein 1 (Dexras1) and Ras homolog enriched in striatum (RHES) are the two monomeric small G proteins that belong to Ras superfamily. These two proteins show 62% similarity. Both of these proteins are involved in signaling and modulation of several pathophysiological processes. They have unique GTP binding domain and a unique C and N terminus. C terminus is known to interact with several proteins; however, the role of its unique N terminus is still not known. The three-dimensional (3D) structure of these proteins is also not available in any of the databases yet. This present study approaches bioinformatics tools and servers to predict the 3D structure of these two proteins in silico.Methods: In this study, two bioinformatics servers were used, namely Swiss modeling server and Iterative Threading ASSEmbly Refinement (I-TASSER) server.Results: Both servers developed many alignment templates of Dexras1 and RHES. These alignments were used to develop 3D structure using Pymol. These models have different regions of proteins such as N terminus, GTP-binding domains, effector loop, C terminus, and the unique CAAX site. The models deduce that the N-terminals of both Dexras1 and RHES are unique regions that might possible be dangling out of the protein while it gets inserted into the membrane. We hypothesize that this unique N-terminal might have a distinct role in the modulation of N-type calcium channels.Conclusion: All the models generated show predicted 3D structure of Dexras1 and RHES protein. This study of structural prediction will be helpful in knowing the interaction of Dexras1 and RHES and a step forward to target these two proteins as a novel therapeutic drug.
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