Critical Reviews in Eukaryotic Gene Expression (CRIT REV EUKAR GENE )

Publisher: Begell House


Critical Reviews in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our understanding of gene regulation, organization, and structure. The journal provides in-depth critical reviews of the current literature on a well-defined topic of immediate interest, written by recognized specialists in the field. Extensive reference lists accompany all articles, providing a comprehensive information resource. The contributions of molecular, cellular, biochemical, and genetic approaches to eukaryotic gene expression are incorporated into each review. The relationship between gene structure and function is stressed, with emphasis on coordinate control of biological processes. Regulatory mechanisms are explored from the perspective of sequences and regulatory molecules that influence structure and expression of eukaryotic genes, as well as within the context of cellular architecture and its relationship to development of cell specialization and tissue organization.

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    Critical Reviews in Eukaryotic Gene Expression website
  • Other titles
    Critical reviews in eukaryotic gene expression, Eukaryotic gene expression
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Begell House

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    • Deposit in institutional repositories is not allowed
    • NIH Authors can deposit in PubMed Central for public release after 12 month embargo
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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Changes of the level and ratios of pyridine nucleotides determine metabolism- dependent cellular redox status and the activity of poly(ADP-ribose) polymerases (PARPs) and sirtuins, thereby influencing several processes closely related to cell survival and death. Pyridine nucleotides participate in numerous metabolic reactions whereby their net cellular level remains constant, but the ratios of NAD+/NADP+ and NADH/NADPH oscillate according to metabolic changes in response to diverse stress signals. In non-redox reactions, NAD+ is degraded and quickly, afterward, resynthesized in the NAD+ salvage pathway, unless overwhelming activation of PARP-1 consumes NAD+ to the point of no return, when the cell can no longer generate enough ATP to accommodate NAD+ resynthesis. The activity of PARP-1 is mandatory for the onset of cytoprotective autophagy on sublethal stress signals. It has become increasingly clear that redox status, largely influenced by the metabolism-dependent composition of the pyridine nucleotides pool, plays an important role in the synthesis of pro-apoptotic and anti-apoptotic sphingolipids. Awareness of the involvement of the prosurvival sphingolipid, sphingosine-1-phosphate, in transition from inflammation to malignant transformation has recently emerged. Here, the participation of pyridine nucleotides in redox and non-redox reactions, sphingolipid metabolism, and their role in cell fate decisions is reviewed.
    Critical Reviews in Eukaryotic Gene Expression 10/2014; 24(4):287-309.
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    ABSTRACT: A full-atom structure of a protein provides an important piece of information for molecular biologists, but has to be complemented by further knowledge concerning its conformational mobility and functional properties. Some scholars have proposed to integrate proteomics-derived data (mainly obtained with techniques like X-ray and NMR crystallography) with protein bioinformatics and computational approaches, above all molecular dynamics (MD), in order to gain better elucidations about proteins. MD simulations have been applied to different areas of protein sciences, but so far little efforts have been made to couple MD with an understanding of the different crystallization techniques which have been proposed during the decades, like classical vapor diffusion hanging drop and its variants (such as sitting drop), in space- and LB (Langmuir-Blodgett)-based crystallization procedures. Using MD, here we show that the optimal protein crystallization techniques prove to be significantly those based on LB-nanotemplate and on in space when compared to the classical vapour diffusion hanging drop and its variants.
    Critical Reviews in Eukaryotic Gene Expression 10/2014; 24(4).
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    ABSTRACT: Crystallization is a highly demanding and time-consuming task, being a real bottle-neck in the nowadays basic research. Several efforts have been made in order to understand which factors and parameters can influence this process and how to finely tune these parameters, facilitating and enabling crystal growth. Different crystallization techniques have been proposed during the decades, like among the others classical vapor hanging drop and its variant (sitting drop), dialysis, cryo-temperature, gel, batch, and even in space (using techniques like free interface diffusion or FID, counter-ion diffusion or CID). Here we present a review of the strategies for obtaining optimal high quality crystals utilizing Langmuir-Blodgett or LB-based nanotechnologies, and space, as proven by Molecular Dynamics (MD) and bioinformatics approaches, namely clustering algorithm and protein alignment.
    Critical Reviews in Eukaryotic Gene Expression 10/2014; 24(4).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Crystallization is a highly demanding and time-consuming task that causes a real bottle-neck in basic research. Great effort has been made to understand the factors and parameters that influence this process and to finely tune them to facilitate crystal growth. Different crystallization techniques have been proposed over the past decades, such as the classical vapor hanging drop method, its variant the sitting drop method, dialysis, cryo-temperature, gel, batch, and the innovative microgravity (space) techniques like free interface diffusion (FID) and counter-ion diffusion (CID). Here, we present a review of the strategies utilizing Langmuir-Blodgett (LB)-based nanotechnologies, and microgravity techniques for obtaining optimal high-quality crystals, as proven by molecular dynamics (MD) and bioinformatics approaches, namely using a clustering algorithm and protein alignment.
    Critical Reviews in Eukaryotic Gene Expression 01/2014; 24(4):325-39.
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    ABSTRACT: Nearly 20% of all breast cancer cases are ductal carcinoma in situ (DCIS), with over 60,000 cases diagnosed each year. Many of these cases would never cause clinical symptoms or threaten the life of the woman; however, it is currently impossible to distinguish which lesions will progress to invasive disease from those that will not. DCIS is generally associated with an excellent prognosis regardless of the treatment pathway, but there is variation in treatment aggressiveness that seems to exceed the medical uncertainty associated with DCIS management. Therefore, it would seem that a significant proportion of women with DCIS receive more extensive treatment than is needed. This overtreatment of DCIS is a growing concern among the breast cancer community and has implications for both the patient (via adverse treatment-related effects, as well as out-of-pocket costs) and society (via economic costs and the public health and environmental harm resulting from health care delivery). This article discusses DCIS treatment pathways and their implications for patients and society and calls for further research to examine the factors that are leading to such wide variation in treatment decisions.
    Critical Reviews in Eukaryotic Gene Expression 01/2014; 24(4):281-6.
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    ABSTRACT: Although considerable controversy surrounds the legitimacy of acupuncture as a treatment, a growing literature on the physiological effects of acupuncture needling in animals and humans is providing new insights into basic cellular mechanisms including connective tissue mechanotransduction and purinergic signaling. This review summarizes these findings and proposes a model combining connective tissue plasticity and peripheral sensory modulation in response to the sustained stretching of tissue that results from acupuncture needle manipulation.
    Critical Reviews in Eukaryotic Gene Expression 01/2014; 24(3):249-53.
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    ABSTRACT: Alternative splicing of precursors messenger RNA (pre-mRNA) is commonly used to increase the diversity of messenger RNAs expressed by the genome in normal multicellular organisms. Dysregulation of alternative splicing underlies a number of human diseases, including cancers. Increasing evidence supports the important role of this expansive layer of gene regulation in hepatocarcinogenesis. Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide because of its aggressive property and limited therapeutic options. Studies suggest that aberrant alternative splicing promotes generation of oncogenic variants in HCC, whereas tumor suppressors are self-inactivated by aberrant alternative splicing in HCC. Moreover, different spliced variants of the same gene can display distinct and even antagonistic biological functions in HCC. As a result, inhibiting the splicing of oncogenic variants and the self-inactivation of tumor suppressors are likely to be new therapy strategies. This review provides a perspective of the emerging evidence of both alternative splicing as a critical mechanism for the development of HCC and that potential cross-talk through signaling pathways among different variants might aid in the development of novel molecular targets of HCC.
    Critical Reviews in Eukaryotic Gene Expression 01/2014; 24(2):133-49.
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    ABSTRACT: Cytoskeleton is one of the essential forms of protein, important in the existence of both eukaryotic as well as prokaryotic cells. Its transformation plays a vital role in cell division and intracellular transportation by facilitating intracellular vesicular traffic. Among the various tissue types in the body, the neural tissue exhibits the maximum heterogeneity, and hence the role of cytoskeleton at both developmental and functional levels becomes paramount. Cytoskeleton dynamics have been established in the neural physiology, but only at the level of axonal development and growth. Retina has not been adequately studied in the context of cytoskeletal proteins.
    Critical Reviews in Eukaryotic Gene Expression 01/2014; 24(3):255-68.
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    ABSTRACT: The GCN5-related N-acetyltransferase (GNAT) superfamily of proteins, widespread in eukaryotes and prokaryotes, can utilize acyl coenzyme A (acyl CoA) to acylate respective acceptor substrates and release both CoA and the acylated products. GNATs have been shown to be involved in multiple physiological events, including bacterial drug resistance, regulation of transcription, stress reaction, and metabolic flux, etc. In the last few years, the importance of GNATs has only emerged in eukaryotes, but bacterial GNATs, particularly those of pathogens, have only recently been explored. In this review, we summarize the main members, structures, inhibitors, and activators of proteins in the GNAT family. We focus on the roles of GNATs in bacteria, particularly Mycobacterium tuberculosis GNATs.
    Critical Reviews in Eukaryotic Gene Expression 01/2014; 24(1):77-87.
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    ABSTRACT: Poly (ADP-ribose) polymerases (PARPs) are a family of related enzymes that share the ability to catalyze the transfer of ADP-ribose to target proteins. PARPs play an important role in various cellular processes, including modulation of chromatin structure, transcription, replication, recombination, and DNA repair. The role of PARP proteins in DNA repair is of particular interest, in view of the finding that certain tumors defective in homologous recombination mechanisms, may rely on PARP-mediated DNA repair for survival, and are sensitive to its inhibition. PARP inhibitors may also increase tumor sensitivity to DNA-damaging agents. Clinical trials of PARP inhibitors are investigating the utility of these approaches in cancer. The hyperactivation of PARP has also been shown to result in a specific programmed cell death pathway involving NAD+/ATP depletion, mu-calpain activation, loss of mitochondrial membrane potential, and the release of apoptosis inducing factor. Hyperactivation of the PARP pathway may be exploited to selectively kill cancer cells. Other PARP forms, including tankyrase 1 (PARP 5a), which plays an important role in enhancing telomere elongation by telomerase, have been found to be potential targets in cancer therapy. The PARP pathway and its inhibition thus offers a number of opportunities for therapeutic intervention in both cancer and other disease states.
    Critical Reviews in Eukaryotic Gene Expression 01/2014; 24(1):15-28.
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    ABSTRACT: Despite significant promise, the routine usage of suspension cell culture to manufacture stem cell-derived differentiated cells has progressed slowly. Suspension culture is an innovative way of either expanding or differentiating cells and sometimes both are combined into a single bioprocess. Its advantages over static 2D culturing include a homogeneous and controllable culture environment and producing a large quantity of cells in a fraction of time. This feature makes suspension cell culture ideal for use in stem cell research and eventually ideal in the large-scale production of differentiated cells for regenerative medicine. Because of their tremendous differentiation capacities and unlimited growth properties, pluripotent stem cells (PSCs) in particular are considered potential sources for future cell-replacement therapies. Currently, expansion of PSCs is accomplished in 2D, which only permits a limited amount of cell growth per culture flask before cells need to be passaged. However, before stem cells can be applied clinically, several aspects of their expansion, such as directed growth, but also differentiation, need to be better controlled. This review will summarize recent advantages in suspension culture of PSCs, while at the same time highlighting current challenges.
    Critical Reviews in Eukaryotic Gene Expression 01/2014; 24(1):1-13.
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    ABSTRACT: Chronic infection with hepatitis B virus is a cause of end-stage liver disease and hepatocellular carcinoma (HCC). We previously screened fructose-bisphosphate aldolase B (ALDOB) as a candidate binding protein of hepatitis B surface antigen (HBsAg) using a yeast 2-hybrid assay. In this study we aimed to confirm ALDOB as a binding protein of the S region of the HbsAg (HBs) and to investigate the function and involved mechanism between its interactions during HCC development. Our results demonstrated that both of exogenous and endogenous ALDOB proteins bind to HBs and colocalize in the cytoplasm in vitro. The coexistence of HBs and ALDOB inhibit apoptosis of cisplatin-induced HepG2 cells. Furthermore, western blot analysis showed the coexistence of HBs and ALDOB enhance the phosphorylations of AKT and its downstream of GSK-3β (phosphorylation); decreased expression of the pro-apoptotic proteins Bax, Bid, Bim, and Puma; and increased expression of the prosur-vival proteins Bcl-2, Bcl-xl, and Mcl-1 in HepG2 cells. These findings suggest that interaction between HBs and ALDOB might be applied as a potential therapeutic target during the treatment of HBV-related hepatitis or HCC.
    Critical Reviews in Eukaryotic Gene Expression 01/2014; 24(3):181-91.
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    ABSTRACT: During lactation, functionally differentiated mammary epithelial cells convert circulating nutrients into various milk components, providing all essential nutrients for the growth and development of mammal neonates. One of the major milk components is milk protein, which includes the casein and whey proteins. Regulation of milk protein gene expression is dependent on hormonal and developmental cues that modulate the activity of specific transcription factors and change the chromatin structure in mammary epithelial cells. Understanding the underlying mechanisms involved in mammary-specific milk protein gene regulation will help improve the yield, quality, and efficiency of milk production and identify important signaling factors and pathways involved in mammary development, differentiation, lactation, and disease. In this review we first review advances in the understanding of the regulatory mechanisms of milk protein genes by hormones, growth factors, and the extracellular matrix, with a focus on transcriptional regulation. We then discuss the relationship between chromatin structure and milk protein gene expression from an epigenetic perspective. Finally, we summarize recent achievements using the mammary gland as a bioreactor for producing pharmaceutical proteins for human use.
    Critical Reviews in Eukaryotic Gene Expression 01/2014; 24(4):357-78.
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    ABSTRACT: MiRNAs regulate gene expression by binding predominantly to the 3' untranslated region (UTR) of target transcripts to prevent their translation and/or induce target degradation. In addition to the more than 1200 human miRNAs, human DNA tumor viruses such as Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) encode miRNAs. Target predictions indicate that each miRNA targets hundreds of transcripts, many of which are regulated by multiple miRNAs. Thus, target identification is a big challenge for the field. Most methods used currently investigate single miRNA-target interactions and are not able to analyze complex miRNA-target networks. To overcome these challenges, cross-linking and immunoprecipitation (CLIP), a recently developed method to study direct RNA-protein interactions in living cells, has been successfully applied to miRNA target analysis. It utilizes Argonaute (Ago)-immunoprecipitation to isolate native Ago-miRNA-mRNA complexes. In four recent publications, two variants of the CLIP method (HITS-CLIP and PAR-CLIP) were utilized to determine the targetomes of human and viral miRNAs in cells infected with the gamma-herpesviruses KSHV and EBV, which are associated with a number of human cancers. Here, we briefly introduce herpesvirus-encoded miRNAs and then focus on how CLIP technology has largely impacted our understanding of viral miRNAs in viral biology and pathogenesis.
    Critical Reviews in Eukaryotic Gene Expression 01/2014; 24(2):101-116.
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    ABSTRACT: Gastric cancer (GC) is common worldwide and has a high rate of metastasis. The underlying molecular mechanism of metastasis are not entirely clear. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression post-transcriptionally and are reported to be involved in multiple steps of tumor metastasis. Clarifying their roles in GC metastasis will improve understanding of this disease. Here, we review the involvement of miRNAs in multiple steps of GC metastasis, including epithelial-mesenchymal transitions, anoikis, angiogenesis, invasion, and migration. The clinical application of miRNAs as prognostic biomarkers in GC is also discussed.
    Critical Reviews in Eukaryotic Gene Expression 01/2014; 24(1):39-53.
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    ABSTRACT: Efflux pump systems are important in general drug resistance. Understanding efflux pumps can inform drug target selection and novel antibiotics designs. In this review, we have summarized the physiological roles, types, and mechanisms of drug efflux pumps. Mycobacterium tuberculosis is the causative agent of tuberculosis, a global threat to public health, and the increasing resistance of this mycobacterium to antibiotics is alarming. Therefore, we have focused on the comparative genomics of efflux pumps and relevant transcriptional regulators of M. tuberculosis.
    Critical Reviews in Eukaryotic Gene Expression 01/2014; 24(2):163-180.
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    ABSTRACT: Many bacteria can develop biofilm (BF), a multicellular structure largely combining bacteria and their extracellular polymeric substances (EPS). The formation of biofilm results in an alternative existence in which microbes ensure their survival in adverse environments. Biofilm-relevant infections are more persistent, resistant to most antibiotics, and more recalcitrant to host immunity. Mycobacterium tuberculosis, the causative agent of tuberculosis, can develop biofilm, though whether M. tuberculosis can form biofilm within tuberculosis patients has yet to be determined. Here, we summarize the factors involved in the development and dispersal of mycobacterial biofilms, as well as underlying regulatory factors and inhibitors against biofilm to deepen our understanding of their development and to elucidate potential novel modes of action for future antibiotics. Key factors in biofilm formation identified as drug targets represent a novel and promising avenue for developing better antibiotics.
    Critical Reviews in Eukaryotic Gene Expression 01/2014; 24(3):269-79.