{"title":"Recent Trends in Eukaryotic Transcription: Crucial Role of Gene Architecture in Transcriptional Regulation","authors":"","doi":"10.13188/2325-4653.1000007","DOIUrl":"https://doi.org/10.13188/2325-4653.1000007","url":null,"abstract":"The Human Genome Project has identified more than 25,000 genes in our cells. Not all of these genes are expressed at the same time or in every cell of our body. A fundamental question in gene expression is how the coordinated expression of genes is achieved during growth, development and homeostasis. The expression of genetic information is regulated to a great extent at the level of transcription. In eukaryotes, RNA polymerase II is the main transcription enzyme, which transcribes protein coding genes and a number of non-coding RNAs. The transcription by RNA polymerase II is regulated by cis-acting DNA elements and trans-acting accessory protein factors. The enhancer, promoter and terminator are the most important DNA elements required for transcription by RNA polymerase II, while accessory protein factors include gene-specific transcription factors, the general transcription factors and termination factors. The generally accepted view is that the factors occupying the promoter region play a dedicated role in initiation of transcription and those operating at the terminator end are exclusively required for the termination step of transcription. The research in my and other laboratories has challenged this dogma.","PeriodicalId":90212,"journal":{"name":"Journal of cytology & molecular biology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42873253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hanaa K B Motawea, Alisa D Blazek, Matthew J Zirwas, Adam P Pleister, Amany A E Ahmed, Bradley K McConnell, Maqsood A Chotani
{"title":"Delocalization of Endogenous A-kinase Antagonizes Rap1-Rho-α<sub>2C</sub>-Adrenoceptor Signaling in Human Microvascular Smooth Muscle Cells.","authors":"Hanaa K B Motawea, Alisa D Blazek, Matthew J Zirwas, Adam P Pleister, Amany A E Ahmed, Bradley K McConnell, Maqsood A Chotani","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The second messenger cyclic AMP (cAMP) plays a vital role in the physiology of the cardiovascular system, including vasodilation of large blood vessels. This study focused on cAMP signaling in peripheral blood vessels, specifically in human vascular smooth muscle (microVSM) cells explanted from skin punch biopsy arterioles (also known as resistance vessels) of healthy volunteers. Using these human microVSM we recently demonstrated cAMP activation of exchange protein activated by cAMP (Epac), the Ras-related small GTPase Rap1A, and RhoA-ROCK-F-actin signaling in human microVSM to increase expression and cell surface translocation of functional α<sub>2C</sub>-adrenoceptors (α<sub>2C</sub>-ARs) that mediate vasoconstriction. Protein-protein association with the actin-binding protein filamin-2 and phosphorylation of filamin-2 Ser<sup>2113</sup> by cAMP-Rap1A-Rho-ROCK signaling were necessary for receptor translocation in these cells. Although cAMP activated A-kinase in these cells, these effects were independent of A-kinase, and suggested compartmentalized A-kinase local signaling facilitated by A-kinase anchoring proteins (AKAPs). In this study we globally disrupted A-kinase-AKAP interactions by the anchoring inhibitor decoy peptide Ht31 and examined the effect on α<sub>2C</sub>-AR expression, translocation, and function in quiescent microVSM treated with the adenylyl cyclase activator and cAMP elevating agent forskolin. The results show that Ht31, but not the control peptide Ht31-P, reduced forskolin-stimulated Ser<sup>133</sup> phosphorylation of A-kinase substrate CREB, reduced α<sub>2C</sub>-AR mRNA levels, reduced cell surface translocated receptors, and attenuated agonist-triggered receptor functional responses. Together, the results suggest that compartmentalized cAMP signaling elicits a selective cellular response in microVSM, which may have relevance to arteriole physiological function and responses.</p>","PeriodicalId":90212,"journal":{"name":"Journal of cytology & molecular biology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970818/pdf/nihms560468.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32236233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abul K Azad, Murugesan V S Rajaram, Larry S Schlesinger
{"title":"Exploitation of the Macrophage Mannose Receptor (CD206) in Infectious Disease Diagnostics and Therapeutics.","authors":"Abul K Azad, Murugesan V S Rajaram, Larry S Schlesinger","doi":"10.13188/2325-4653.1000003","DOIUrl":"https://doi.org/10.13188/2325-4653.1000003","url":null,"abstract":"The macrophage mannose receptor (MR, CD206) is a C-type lectin expressed predominantly by most tissue macrophages, dendritic cells and specific lymphatic or endothelial cells. It functions in endocytosis and phagocytosis, and plays an important role in immune homeostasis by scavenging unwanted mannoglycoproteins. More attention is being paid to its particularly high expression in tissue pathology sites during disease such the tumor microenvironment. The MR recognizes a variety of microorganisms by their mannan-coated cell wall, which is exploited by adapted intracellular pathogens such as Mycobacterium tuberculosis, for their own survival. Despite the continued development of drug delivery technologies, the targeting of agents to immune cells, especially macrophages, for effective diagnosis and treatment of chronic infectious diseases has not been addressed adequately. In this regard, strategies that optimize MR-mediated uptake by macrophages in target tissues during infection are becoming an attractive approach. We review important progress in this area.","PeriodicalId":90212,"journal":{"name":"Journal of cytology & molecular biology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.13188/2325-4653.1000003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32212760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Current Understanding and Future Directions for Vocal Fold Mechanobiology.","authors":"Nicole Y K Li, Hossein K Heris, Luc Mongeau","doi":"10.13188/2325-4653.1000001","DOIUrl":"10.13188/2325-4653.1000001","url":null,"abstract":"<p><p>The vocal folds, which are located in the larynx, are the main organ of voice production for human communication. The vocal folds are under continuous biomechanical stress similar to other mechanically active organs, such as the heart, lungs, tendons and muscles. During speech and singing, the vocal folds oscillate at frequencies ranging from 20 Hz to 3 kHz with amplitudes of a few millimeters. The biomechanical stress associated with accumulated phonation is believed to alter vocal fold cell activity and tissue structure in many ways. Excessive phonatory stress can damage tissue structure and induce a cell-mediated inflammatory response, resulting in a pathological vocal fold lesion. On the other hand, phonatory stress is one major factor in the maturation of the vocal folds into a specialized tri-layer structure. One specific form of vocal fold oscillation, which involves low impact and large amplitude excursion, is prescribed therapeutically for patients with mild vocal fold injuries. Although biomechanical forces affect vocal fold physiology and pathology, there is little understanding of how mechanical forces regulate these processes at the cellular and molecular level. Research into vocal fold mechanobiology has burgeoned over the past several years. Vocal fold bioreactors are being developed in several laboratories to provide a biomimic environment that allows the systematic manipulation of physical and biological factors on the cells of interest <i>in vitro</i>. Computer models have been used to simulate the integrated response of cells and proteins as a function of phonation stress. The purpose of this paper is to review current research on the mechanobiology of the vocal folds as it relates to growth, pathogenesis and treatment as well as to propose specific research directions that will advance our understanding of this subject.</p>","PeriodicalId":90212,"journal":{"name":"Journal of cytology & molecular biology","volume":"1 1","pages":"001"},"PeriodicalIF":0.0,"publicationDate":"2013-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011392/pdf/nihms490792.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32328401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}