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Expression Analysis of RbBP6 in human cancers: a Prospective biomarker.
Mbita, Z, Hull, R, Mbele, M, Makhafola, T, Dlamini, Z
Anti-cancer drugs. 2019;(8):767-773
Abstract
Retinoblastoma binding protein 6 (RBBP6) is a cancer-related protein that has been implicated in the regulation of cell cycle and apoptosis. RBBP6 isoform 1 has been demonstrated to interact with two tumour suppressors, p53 and pRB. Isoform 1 been shown to regulate p53 through its ubiquitin ligase activity, thus implicating in cell cycle regulation and apoptosis. Isoforms 1 and 2 are multidomain proteins containing a domain with no name (DWNN) domain, a Zinc Finger, a RING Finger, an Rb-binding domain and a p53-binding domain. The RBBP6 isoform 3 comprises the DWNN domain only. Isoform 4 lacks the Rb-binding domain but its role is less understood. RBBP6 isoform 3 has been reported as a cell cycle regulator with anticancer potential. There have been several studies that have clearly demonstrated that RBBP6 may be an important biomarker for cancer diagnosis and a potential drug target for cancer treatment. This work focused on differential expression of RBBP6 transcripts in different cancers, providing detailed analysis of their potential as diagnostic biomarkers for different cancers. These cancers include breast, liver, cervical and colon carcinomas. The expression of RBBP6 transcripts may further provide better understanding of the role of the RBBP6 in carcinogenesis and cell homeostasis.
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The role of new adipokines in gestational diabetes mellitus pathogenesis.
Mierzyński, R, Poniedziałek-Czajkowska, E, Dłuski, D, Leszczyńska-Gorzelak, B
Ginekologia polska. 2018;(4):221-26
Abstract
Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition dur-ing pregnancy. Explanation of the GDM pathogenesis is important due to preventing gestational complications. During pregnancy there are significant changes in maternal metabolism. Many of these changes are influenced by different adi-pokines produced in the placenta and adipose tissue. The exact role of adipokines in the pathogenesis of GDM remains still unknown. Several adipokines have been analysed throughout gestation and their levels have been suggested as biomarkers of maternal-perinatal outcomes. Some of them have been postulated as significant in the pathogenesis of pregnancy complications like GDM. This report aims to review some of the recent topics of adipokine research that may be of particular importance in patho-physiology and diagnosis of gestational diabetes mellitus. Because of manuscript length limitations, after thorough literature review and in view of the recent evidence, we focus on the one of the most well-known adipokine: adiponectin, and not so well-studied: nesfatin-1, chemerin, ghrelin, and CTRP 1.
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A minireview of E4BP4/NFIL3 in heart failure.
Velmurugan, BK, Chang, RL, Marthandam Asokan, S, Chang, CF, Day, CH, Lin, YM, Lin, YC, Kuo, WW, Huang, CY
Journal of cellular physiology. 2018;(11):8458-8466
Abstract
Heart failure (HF) remains a major cause of morbidity and mortality worldwide. The primary cause identified for HF is impaired left ventricular myocardial function, and clinical manifestations may lead to severe conditions like pulmonary congestion, splanchnic congestion, and peripheral edema. Development of new therapeutic strategies remains the need of the hour for controlling the problem of HF worldwide. Deeper insights into the molecular mechanisms involved in etiopathology of HF indicate the significant role of calcium signaling, autocrine signaling pathways, and insulin-like growth factor-1 signaling that regulates the physiologic functions of heart growth and development such as contraction, metabolism, hypertrophy, cytokine signaling, and apoptosis. In view of these facts, a transcription factor (TF) regulating the myriad of these signaling pathways may prove as a lead candidate for development of therapeutics. Adenovirus E4 promoter-binding protein (E4BP4), also known as nuclear-factor, interleukin 3 regulated (NFIL3), a type of basic leucine zipper TF, is known to regulate the signaling processes involved in the functioning of heart. The current review discusses about the expression, structure, and functional role of E4BP4 in signaling processes with emphasis on calcium signaling mechanisms, autocrine signaling, and insulin-like growth factor II receptor-mediated processes regulated by E4BP4 that may regulate the pathogenesis of HF. We propose that E4BP4, being the critical component for the regulation of the above signaling processes, may serve as a novel therapeutic target for HF, and scientific investigations are merited in this direction.
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4.
Targeting ZBP-89 for the treatment of hepatocellular carcinoma.
Wang, N, Wang, S, Yang, SL, Liu, LP, Li, MY, Lai, PBS, Chen, GG
Expert opinion on therapeutic targets. 2018;(10):817-822
Abstract
Zinc-binding protein-89 (ZBP-89) is a Krüppel-type zinc-finger transcription factor that regulates target gene expression profiles via directly binding to GC-rich gene promoters, recruiting chromatin modifiers or by interacting with other proteins. The importance of ZBP-89 in the regulation of cell cycle arrest and apoptosis has led to increased interest and investigations for its role in cancer development. Areas covered: We describe ZBP-89 as a candidate therapeutic target for hepatocellular carcinoma (HCC) from several perspectives. ZBP-89 can upregulate apoptosis in HCC in a p53-dependent or - independent manner. In addition, the negative regulation of ZBP-89 on liver cancer stemness sheds light on its possible effect on sensitizing HCC to chemotherapies and the reduction of HCC relapse. The prognostic significance of ZBP-89 in HCC patients further suggests its clinical importance as a potential tumor suppressor. Expert opinion: Given the roles of ZBP-89 in HCC, we believe, ZBP-89 is a promising therapeutic target for enhancing apoptosis and diminishing the liver cancer stemness. At the same time, we also face a series of challenges, especially in the clinical implication of ZBP-89. Resolving the current controversies will advance the development of ZBP-89 for anti-HCC therapy.
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5.
CIN-TCP transcription factors: Transiting cell proliferation in plants.
Sarvepalli, K, Nath, U
IUBMB life. 2018;(8):718-731
Abstract
Leaves are the most conspicuous planar organs in plants, designed for efficient capture of sunlight and its conversion to energy that is channeled into sustaining the entire biosphere. How a few founder cells derived from the shoot apical meristem give rise to diverse leaf forms has interested naturalists and developmental biologists alike. At the heart of leaf morphogenesis lie two simple cellular processes, division and expansion, that are spatially and temporally segregated in a developing leaf. In leaves of dicot model species, cell division occurs predominantly at the base, concomitant with the expansion and differentiation of cells at the tip of the lamina that drives increase in leaf surface area. The timing of the transition from one cell fate (division) to the other (expansion) within a growing leaf lamina is a critical determinant of final leaf shape, size, complexity and flatness. The TCP proteins, unique to plant kingdom, are sequence-specific DNA-binding transcription factors that control several developmental and physiological traits. A sub-group of class II TCPs, called CINCINNATA-like TCPs (CIN-TCPs henceforth), are key regulators of the timing of the transition from division to expansion in dicot leaves. The current review highlights recent advances in our understanding of how the pattern of CIN-TCP activity is translated to the dynamic spatio-temporal control of cell-fate transition through the transactivation of cell-cycle regulators, growth-repressing microRNAs, and interactions with the chromatin remodeling machinery to modulate phytohormone responses. Unravelling how environmental inputs influence CIN-TCP-mediated growth control is a challenge for future studies. © 2018 IUBMB Life, 70(8):718-731, 2018.
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Novel transmitters in brain stem vagal neurocircuitry: new players on the pitch.
Bülbül, M, Travagli, RA
American journal of physiology. Gastrointestinal and liver physiology. 2018;(1):G20-G26
Abstract
The last few decades have seen a major increase in the number of neurotransmitters and neuropeptides recognized as playing a role in brain stem neurocircuits, including those involved in homeostatic functions such as stress responsiveness, gastrointestinal motility, feeding, and/or arousal/wakefulness. This minireview will focus on the known physiological role of three of these novel neuropeptides, i.e., apelin, nesfatin-1, and neuropeptide-S, with a special emphasis on their hypothetical roles in vagal signaling related to gastrointestinal motor functions.
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7.
Stress response factors drive regrowth of quiescent cells.
Kuang, Z, Ji, H, Boeke, JD
Current genetics. 2018;(4):807-810
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Abstract
Quiescent cells exploit an array of transcription factors to activate stress response machinery and maintain survival under nutrient-limited conditions. Our recent findings reveal that these transcription factors also play an important role in the exit of quiescence and regrowth. By studying Saccharomyces cerevisiae under a continuous, nutrient-limited condition, we found that Msn2 and Msn4 function as master regulators of glycolytic genes in the quiescent-like phase. They control the timing of transition from quiescence to growth by regulating the accumulation rate of acetyl-CoA, a key metabolite that is downstream of glycolysis and drives growth. These findings suggest a model that Msn2/4 not only protect the cells from starvation but also facilitate their regrowth from quiescence. Thus, understanding the functions of stress response transcription factors in metabolic regulation will provide deeper insight into how quiescent cells manage the capacity of regrowth.
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The SWI/SNF chromatin-remodeling factors BAF60a, b, and c in nutrient signaling and metabolic control.
Wang, RR, Pan, R, Zhang, W, Fu, J, Lin, JD, Meng, ZX
Protein & cell. 2018;(2):207-215
Abstract
Metabolic syndrome has become a global epidemic that adversely affects human health. Both genetic and environmental factors contribute to the pathogenesis of metabolic disorders; however, the mechanisms that integrate these cues to regulate metabolic physiology and the development of metabolic disorders remain incompletely defined. Emerging evidence suggests that SWI/SNF chromatin-remodeling complexes are critical for directing metabolic reprogramming and adaptation in response to nutritional and other physiological signals. The ATP-dependent SWI/SNF chromatin-remodeling complexes comprise up to 11 subunits, among which the BAF60 subunit serves as a key link between the core complexes and specific transcriptional factors. The BAF60 subunit has three members, BAF60a, b, and c. The distinct tissue distribution patterns and regulatory mechanisms of BAF60 proteins confer each isoform with specialized functions in different metabolic cell types. In this review, we summarize the emerging roles and mechanisms of BAF60 proteins in the regulation of nutrient sensing and energy metabolism under physiological and disease conditions.
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Antioxidative Phytochemicals Accelerate Epidermal Terminal Differentiation via the AHR-OVOL1 Pathway: Implications for Atopic Dermatitis.
Furue, M, Hashimoto-Hachiya, A, Tsuji, G
Acta dermato-venereologica. 2018;(10):918-923
Abstract
Aryl hydrocarbon receptor (AHR) is a chemical sensor that is expressed abundantly in epidermal keratinocytes. Oxidative AHR ligands induce the production of reactive oxygen species. However, antioxidant AHR ligands inhibit reactive oxygen species generation via activation of nuclear factor-erythroid 2-related factor-2, which is a master switch for antioxidative signalling. In addition, AHR signalling accelerates epidermal terminal differentiation, but excessive acceleration by oxidative ligands, such as dioxins, may induce chloracne and inflammation. However, antioxidative phytochemical ligands induce the beneficial acceleration of epidermal differentiation that repairs skin barrier disruption. The upregulated expression of differentiation molecules, such as filaggrin, is mediated via the AHR-OVOL1 axis. This AHR-OVOL1 system is capable of counteracting skin barrier dysfunction in T-helper type 2-shifted inflammation. This article reviews the dynamic and multifaceted role of AHR in epidermal biology and discusses the potential use of antioxidative phytochemical ligands for AHR in inflammatory skin diseases, such as atopic dermatitis.
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Statins in anthracycline-induced cardiotoxicity: Rac and Rho, and the heartbreakers.
Henninger, C, Fritz, G
Cell death & disease. 2017;(1):e2564
Abstract
Cancer patients receiving anthracycline-based chemotherapy are at risk to develop life-threatening chronic cardiotoxicity with the pathophysiological mechanism of action not fully understood. Besides the most common hypothesis that anthracycline-induced congestive heart failure (CHF) is mainly caused by generation of reactive oxygen species, recent data point to a critical role of topoisomerase II beta (TOP2B), which is a primary target of anthracycline poisoning, in the pathophysiology of CHF. As the use of the only clinically approved cardioprotectant dexrazoxane has been limited by the FDA in 2011, there is an urgent need for alternative cardioprotective measures. Statins are anti-inflammatory and anti-oxidative drugs that are clinically well established for the prevention of cardiovascular diseases. They exhibit pleiotropic beneficial properties beyond cholesterol-lowering effects that most likely rest on the indirect inhibition of small Ras homologous (Rho) GTPases. The Rho GTPase Rac1 has been shown to be a major factor in the regulation of the pro-oxidative NADPH oxidase as well as in the regulation of type II topoisomerase. Both are discussed to play an important role in the pathophysiology of anthracycline-induced CHF. Therefore, off-label use of statins or novel Rac1 inhibitors might represent a promising pharmacological approach to gain control over chronic cardiotoxicity by interfering with key mechanisms of anthracycline-induced cardiomyocyte cell death.