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Michael E Fusakio, Jeffrey A Willy, Yongping Wang, Emily T Mirek, Rana J T Al Baghdadi, Christopher M Adams, Tracy G Anthony, Ronald C Wek
Disturbances in protein folding and membrane compositions in the endoplasmic reticulum (ER) elicit the unfolded protein response (UPR). Each of three UPR sensory proteins-PERK (PEK/EIF2AK3), IRE1, and ATF6-is activated by ER stress. PERK phosphorylation of eIF2 represses global protein synthesis, lowering influx of nascent polypeptides into the stressed ER, coincident with preferential translation of ATF4 (CREB2). In cultured cells, ATF4 induces transcriptional expression of genes directed by the PERK arm of the UPR, including genes involved in amino acid metabolism, resistance to oxidative stress, and the proapoptotic transcription factor CHOP (GADD153/DDIT3)...
May 1, 2016: Molecular Biology of the Cell
Lijie Hao, Zhuoqin Yang, Yuanhong Bi
The cyclic AMP (cAMP)-response element-binding protein (CREB) family of transcription factors is crucial in regulating gene expression required for long-term memory (LTM) formation. Upon exposure of sensory neurons to the neurotransmitter serotonin (5-HT), CREB1 is activated via activation of the protein kinase A (PKA) intracellular signaling pathways, and CREB2 as a transcriptional repressor is relieved possibly via phosphorylation of CREB2 by mitogen-activated protein kinase (MAPK). Song et al. [18] proposed a minimal model with only interlinked positive and negative feedback loops of transcriptional regulation by the activator CREB1 and the repressor CREB2...
April 2016: Mathematical Biosciences
Balasubramanian Senthilkumaran, Gunti Sreenivasulu, De-Shou Wang, Cheni-Chery Sudhakumari, Tohru Kobayashi, Yoshitaka Nagahama
In fish, oocyte meiotic maturation is regulated by 17α, 20β-dihydroxy-progesterone through cAMP. To study the role of cAMP response element binding protein (CREB) in meiotic maturation, we cloned and characterized the expression pattern of CREBs from two fish models, the Nile tilapia and catfish. In the Nile tilapia three different CREBs were identified where in CREB1 was found in many tissues including gonads with abundant expression in testis. CREB2, few amino acids shorter than CREB1, was expressed in several tissues with abundant expression in ovary...
2015: PloS One
Goutham U Raval, Carlo Bidoia, Greta Forlani, Giovanna Tosi, Antoine Gessain, Roberto S Accolla
BACKGROUND: Human T cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of a severe form of neoplasia designated Adult T cell Leukaemia (ATL). It is widely accepted that the viral transactivator Tax-1 is the major viral product involved in the onset, but not in the maintenance, of neoplastic phenotype, as only 30-40% of ATL cells express Tax-1. It has been recently demonstrated that HBZ (HTLV-1 bZIP factor), a protein encoded by the minus strand of HTLV-1 genome, constantly expressed in infected cells and in ATL tumor cells, is also involved in the pathogenesis of leukaemia...
2015: Retrovirology
Patrick K McCamphill, Margaret H Hastings
No abstract text is available yet for this article.
May 27, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Chirine Toufaily, Adjimon Gatien Lokossou, Amandine Vargas, Éric Rassart, Benoit Barbeau
Syncytin-2 is encoded by the envelope gene of Endogenous Retrovirus-FRD (ERVFRD-1) and plays a critical role in fusion of placental trophoblasts leading to the formation of the multinucleated syncytiotrophoblast. Its expression is consequently regulated in a strict manner. In the present study, we have identified a forskolin-responsive region located between positions -300 to -150 in the Syncytin-2 promoter region. This 150 bp region in the context of a minimal promoter mediated an 80-fold induction of promoter activity following forskolin stimulation...
2015: PloS One
Jiang-Yuan Hu, Amir Levine, Ying-Ju Sung, Samuel Schacher
Basic region leucine zipper (bZIP) transcription factors regulate gene expression critical for long-term synaptic plasticity or neuronal excitability contributing to learning and memory. At sensorimotor synapses of Aplysia, changes in activation or expression of CREB1 and CREB2 in sensory neurons are required for long-term synaptic plasticity. However, it is unknown whether concomitant stimulus-induced changes in expression and activation of bZIP transcription factors in the postsynaptic motor neuron also contribute to persistent long-term facilitation (P-LTF)...
January 7, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ling Lin, Zhixing Yao, Krithika Bhuvaneshwar, Yuriy Gusev, Bhaskar Kallakury, Shaoxian Yang, Kirti Shetty, Aiwu Ruth He
The cytoskeletal protein Spectrin, beta, non-erythrocytic 1 (SPTBN1), an adapter protein to SMAD3 in TGF-β signaling, may prevent hepatocellular carcinoma (HCC) development by downregulating the expression of signal transducer and activator of transcription 3 (STAT3). To elucidate the as yet undefined mechanisms that regulate this process, we demonstrate that higher levels of STAT3 transcription are found in livers of heterozygous SPTBN1(+/-) mice as compared to that of wild type mice. We also found increased levels of STAT3 mRNA, STAT3 protein, and p-STAT3 in human HCC cell-lines after knockdown of SPTBN1 or SMAD3, which promoted cell colony formation...
November 2014: Carcinogenesis
Chun-li Song, Ji-hua Ren, Long-kuan Ran, Yong-guo Li, Xiao-song Li, Xiang Chen, Wan-yu Li, Ai-long Huang, Juan Chen
Hepatitis B virus (HBV) infection is the leading cause of liver diseases. However, the molecular mechanisms of HBV infection and carcinogenesis have not been fully elucidated. In this study, we found that cyclin D2 was upregualted in HBV-expressing cells and liver tissues of HBV-transgenic mice. Gene silencing of cyclin D2 inhibited HBV DNA replicative intermediates, 3.5 kb mRNA, core protein level, as well as the secretions of HBsAg and HBeAg. On the contrary, overexpression of cyclin D2 promoted HBV replication...
August 2014: Virology
Yili Zhang, Paul Smolen, Douglas A Baxter, John H Byrne
Cellular functions and responses to stimuli are controlled by complex regulatory networks that comprise a large diversity of molecular components and their interactions. However, achieving an intuitive understanding of the dynamical properties and responses to stimuli of these networks is hampered by their large scale and complexity. To address this issue, analyses of regulatory networks often focus on reduced models that depict distinct, reoccurring connectivity patterns referred to as motifs. Previous modeling studies have begun to characterize the dynamics of small motifs, and to describe ways in which variations in parameters affect their responses to stimuli...
March 2014: PLoS Computational Biology
V A Nunes, E P Portioli-Sanches, M P Rosim, M S Araujo, P Praxedes-Garcia, M M R Valle, L P Roma, C Hahn, E Gurgul-Convey, S Lenzen, A K Azevedo-Martins
Progesterone has been associated with the development of gestational diabetes (GD) due to the enhancement of insulin resistance. As β-cell apoptosis participates in type 1 and type 2 diabetes pathophysiology, we proposed the hypothesis that progesterone might contribute to the development of GD through a mechanism that also involves β-cell death. To address this question, RINm5F insulin-producing cells were incubated with progesterone (25-100 μM), in the presence or absence of α-tocopherol (40 μM)...
May 2014: Journal of Endocrinology
Jingshu Wang, Liqun Liu, Huijuan Qiu, Xiaohong Zhang, Wei Guo, Wangbing Chen, Yun Tian, Lingyi Fu, Dingbo Shi, Jianding Cheng, Wenlin Huang, Wuguo Deng
Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid distributed in medical herbs, exerts antitumor effects and is emerging as a promising compound for cancer prevention and therapy, but its excise mechanisms of action in colon cancer cells remains largely unknown. Here, we identified the molecular mechanisms by which UA inhibited cell proliferation and induced apoptosis in human colon cancer SW480 and LoVo cells. Treatment with UA led to significant inhibitions in cell viability and clone formation and changes in cell morphology and spreading...
2013: PloS One
Alfred Csibi, Sarah-Maria Fendt, Chenggang Li, George Poulogiannis, Andrew Y Choo, Douglas J Chapski, Seung Min Jeong, Jamie M Dempsey, Andrey Parkhitko, Tasha Morrison, Elizabeth P Henske, Marcia C Haigis, Lewis C Cantley, Gregory Stephanopoulos, Jane Yu, John Blenis
Proliferating mammalian cells use glutamine as a source of nitrogen and as a key anaplerotic source to provide metabolites to the tricarboxylic acid cycle (TCA) for biosynthesis. Recently, mammalian target of rapamycin complex 1 (mTORC1) activation has been correlated with increased nutrient uptake and metabolism, but no molecular connection to glutaminolysis has been reported. Here, we show that mTORC1 promotes glutamine anaplerosis by activating glutamate dehydrogenase (GDH). This regulation requires transcriptional repression of SIRT4, the mitochondrial-localized sirtuin that inhibits GDH...
May 9, 2013: Cell
P A Melas, A Lennartsson, H Vakifahmetoglu-Norberg, Y Wei, E Åberg, M Werme, M Rogdaki, M Mannervik, G Wegener, S Brené, A A Mathé, C Lavebratt
Neuropeptide Y (NPY) has been implicated in depression, emotional processing and stress response. Part of this evidence originates from human single-nucleotide polymorphism (SNP) studies. In the present study, we report that a SNP in the rat Npy promoter (C/T; rs105431668) affects in vitro transcription and DNA-protein interactions. Genotyping studies showed that the C-allele of rs105431668 is present in a genetic rat model of depression (Flinders sensitive line; FSL), while the SNP's T-allele is present in its controls (Flinders resistant line; FRL)...
2013: Translational Psychiatry
Priyamvada Rajasethupathy, Igor Antonov, Robert Sheridan, Sebastian Frey, Chris Sander, Thomas Tuschl, Eric R Kandel
Small RNA-mediated gene regulation during development causes long-lasting changes in cellular phenotypes. To determine whether small RNAs of the adult brain can regulate memory storage, a process that requires stable and long-lasting changes in the functional state of neurons, we generated small RNA libraries from the Aplysia CNS. In these libraries, we discovered an unexpectedly abundant expression of a 28 nucleotide sized class of piRNAs in brain, which had been thought to be germline specific. These piRNAs have unique biogenesis patterns, predominant nuclear localization, and robust sensitivity to serotonin, a modulatory transmitter that is important for memory...
April 27, 2012: Cell
Xiangsheng Xiao, Dingbo Shi, Liqun Liu, Jingshu Wang, Xiaoming Xie, Tiebang Kang, Wuguo Deng
Quercetin, a polyphenolic bioflavonoid, possesses multiple pharmacological actions including anti-inflammatory and antitumor properties. However, the precise action mechanisms of quercetin remain unclear. Here, we reported the regulatory actions of quercetin on cyclooxygenase-2 (COX-2), an important mediator in inflammation and tumor promotion, and revealed the underlying mechanisms. Quercetin significantly suppressed COX-2 mRNA and protein expression and prostaglandin (PG) E(2) production, as well as COX-2 promoter activation in breast cancer cells...
2011: PloS One
Sudeshna Das, Madhumala K Sadanandappa, Adrian Dervan, Aoife Larkin, John Anthony Lee, Indulekha P Sudhakaran, Rashi Priya, Raheleh Heidari, Eimear E Holohan, Angel Pimentel, Avni Gandhi, Kei Ito, Subhabrata Sanyal, Jing W Wang, Veronica Rodrigues, Mani Ramaswami
Despite its ubiquity and significance, behavioral habituation is poorly understood in terms of the underlying neural circuit mechanisms. Here, we present evidence that habituation arises from potentiation of inhibitory transmission within a circuit motif commonly repeated in the nervous system. In Drosophila, prior odorant exposure results in a selective reduction of response to this odorant. Both short-term (STH) and long-term (LTH) forms of olfactory habituation require function of the rutabaga-encoded adenylate cyclase in multiglomerular local interneurons (LNs) that mediate GABAergic inhibition in the antennal lobe; LTH additionally requires function of the cAMP response element-binding protein (CREB2) transcription factor in LNs...
September 6, 2011: Proceedings of the National Academy of Sciences of the United States of America
S-H Kim, J K Son, E-M Yang, J-E Kim, H-S Park
BACKGROUND: Urticaria is the commonest cutaneous reaction caused by aspirin or other nonsteroidal anti-inflammatory drugs. The pathogenesis of aspirin-induced urticaria (AIU) is not fully understood, but appears to involve mast cell activation and neutrophil infiltration. OBJECTIVES: To investigate the genetic contribution of interleukin (IL)-18, which can amplify acute inflammation by promoting mast cell activation, neutrophil migration and cytokine production, to the pathogenesis of AIU...
November 2011: British Journal of Dermatology
Rong-Yu Liu, Shreyansh Shah, Leonard J Cleary, John H Byrne
Long-term memory and plasticity, including long-term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse, depend on the activation of transcription factors that regulate genes necessary for synaptic plasticity. In the present study we found that treatment with 5-HT and behavioral training produce biphasic changes in the expression of CREB2, a transcriptional repressor. An immediate increase in CREB2 protein was followed by a subsequent decrease. The effects of these treatments persist for at least 24 h and are observed in isolated sensory neurons...
2011: Learning & Memory
Teng Rhui Lwa, Jialing Lee, Chew Har Ng, Qiao Jing Lew, Hui Ching Hia, Sheng-Hao Chao
The human cytomegalovirus (CMV) major immediate-early (MIE) promoter is widely used in mammalian cells for production of recombinant proteins. It is of great interest to further enhance protein production driven by the CMV promoter. Here, we report that the Tax protein of human T-lymphotropic virus stimulates the transgene expression under the control of CMV MIE promoter in HEK293 cells. At least threefold increases in transient production of recombinant proteins, including luciferase and two biopharmaceutical proteins (erythropoietin and interferon-γ), were detected...
May 2011: Biotechnology Progress
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