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sumo neuron

Robert C A M van Waardenburg
Tyrosyl-DNA phosphodiesterase I (TDP1), like most DNA repair associated proteins, is not essential for cell viability. However, dysfunctioning TDP1 or ATM (ataxia telangiectasia mutated) results in autosomal recessive neuropathology with similar phenotypes, including cerebellar atrophy. Dual inactivation of TDP1 and ATM causes synthetic lethality. A TDP1H(493)R catalytic mutant is associated with spinocerebellar ataxia with axonal neuropathy (SCAN1), and stabilizes the TDP1 catalytic obligatory enzyme-DNA covalent complex...
2016: Journal of Neurology & Neuromedicine
Kazushiro Fujiwara, Koichi Hasegawa, Masahiro Oka, Yoshihiro Yoneda, Kazuaki Yoshikawa
Terminal differentiation of neurons is accompanied by irreversible exit from the cell cycle and expression of neuronal phenotypes. The molecular mechanism whereby committed neuronal progenitors lose their ability to reenter the cell cycle is largely unknown. Here, we report that the nuclear transport system is rapidly remodeled in primary cortical progenitor cells (CPCs) at the very beginning of neuronal terminal differentiation. High levels of Ran GTPase-activating protein 1 (RanGAP), a key regulator of the Ran GTP-GDP cycle, in primary CPCs are drastically reduced upon neuronal induction...
September 22, 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Frauke Liebelt, Alfred C O Vertegaal
Cellular proteomes are continuously undergoing alterations as a result of new production of proteins, protein folding, and degradation of proteins. The proper equilibrium of these processes is known as proteostasis, implying that proteomes are in homeostasis. Stress conditions can affect proteostasis due to the accumulation of misfolded proteins as a result of overloading the degradation machinery. Proteostasis is affected in neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and multiple polyglutamine disorders including Huntington's disease...
August 1, 2016: American Journal of Physiology. Cell Physiology
Silvia Schwartz, Mauro Truglio, Maxwell J Scott, Helen L Fitzsimons
HDAC4 is a potent memory repressor with overexpression of wild type or a nuclear-restricted mutant resulting in memory deficits. Interestingly, reduction of HDAC4 also impairs memory via an as yet unknown mechanism. Although histone deacetylase family members are important mediators of epigenetic mechanisms in neurons, HDAC4 is predominantly cytoplasmic in the brain and there is increasing evidence for interactions with nonhistone proteins, suggesting HDAC4 has roles beyond transcriptional regulation. To that end, we performed a genetic interaction screen in Drosophila and identified 26 genes that interacted with HDAC4, including Ubc9, the sole SUMO E2-conjugating enzyme...
July 2016: Genetics
M Antunica-Noguerol, M L Budziñski, J Druker, N C Gassen, M C Sokn, S Senin, F Aprile-Garcia, F Holsboer, T Rein, A C Liberman, E Arzt
FK506-binding protein 51 (FKBP51) regulates the activity of the glucocorticoid receptor (GR), and is therefore a key mediator of the biological actions of glucocorticoids. However, the understanding of the molecular mechanisms that govern its activity remains limited. Here, we uncover a novel regulatory switch for GR activity by the post-translational modification of FKBP51 with small ubiquitin-like modifier (SUMO). The major SUMO-attachment site, lysine 422, is required for FKBP51-mediated inhibition of GR activity in hippocampal neuronal cells...
October 2016: Cell Death and Differentiation
Joseph Ochaba, Alex Mas Monteys, Jacqueline G O'Rourke, Jack C Reidling, Joan S Steffan, Beverly L Davidson, Leslie M Thompson
The disruption of protein quality control networks is central to pathology in Huntington's disease (HD) and other neurodegenerative disorders. The aberrant accumulation of insoluble high-molecular-weight protein complexes containing the Huntingtin (HTT) protein and SUMOylated protein corresponds to disease manifestation. We previously identified an HTT-selective E3 SUMO ligase, PIAS1, that regulates HTT accumulation and SUMO modification in cells. Here we investigated whether PIAS1 modulation in neurons alters HD-associated phenotypes in vivo...
May 4, 2016: Neuron
Yang-Ja Lee, Joshua D Bernstock, Nandakumar Nagaraja, Brian Ko, John M Hallenbeck
The putative neuroprotective properties of various flavonoids have long been reported. Among this class of chemicals, quercetin, a major flavone/flavonol naturally occurring in plants, deserves focused attention because of the myriad of beneficial effects observed in various in vitro and in vivo models of central nervous system damage/degeneration. However, the mechanisms governing the beneficial outcomes mediated by quercetin remain to be elucidated. In an effort to define the underlying molecular mechanisms, our study employed human/rat neuroblastoma cell lines (SHSY5Y and B35, respectively) and E18-derived rat primary cortical neurons upon which the effects of various flavonoids were examined...
July 2016: Journal of Neurochemistry
Francisco Juarez-Vicente, Noelia Luna-Pelaez, Mario Garcia-Dominguez
Covalent attachment of the Small ubiquitin-like modifier (Sumo) polypeptide to proteins regulates many processes in the eukaryotic cell. In the nervous system, Sumo has been associated with the synapsis and with neurodegenerative diseases. However, its involvement in regulating neuronal differentiation remains largely unknown. Here we show that net Sumo deconjugation is observed during neurogenesis and that Sumo overexpression impairs this process. In an attempt to shed light on the underlying mechanisms, we have analyzed the expression profile of genes coding for components of the sumoylation pathway following induction of neuronal differentiation...
July 2016: Biochimica et Biophysica Acta
Ana Cristina Guerra de Souza, Rui Daniel Prediger, Helena Cimarosti
Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by cardinal motor signs such as rigidity, bradykinesia or rest tremor that arise from a significant death of dopaminergic neurons. Non-dopaminergic degeneration also occurs and it seems to induce the deficits in olfactory, emotional, and memory functions that precede the classical motor symptoms in PD. Despite the majority of PD cases being sporadic, several genes have previously been associated with the hereditary forms of the disease...
June 2016: Journal of Neurochemistry
Hongmei Wu, Xu Chen, Jinke Cheng, Yitao Qi
Neuronal potassium ion channels play an essential role in the generation of the action potential and excitability of neurons. The dysfunction of ion channel subunits can cause channelopathies, which are associated in some cases with sudden unexplained death in epilepsy SUDEP. The physiological roles of neuronal ion channels have been largely determined, but little is known about the molecular mechanisms underlying neurological channelopathies, especially the determinants of the channels' regulation. SUMO (small ubiquitin-like modifier) proteins covalently conjugate lysine residues in a large number of target proteins and modify their functions...
2016: Advances in Protein Chemistry and Structural Biology
Derek J C Tai, Yen C Liu, Wei L Hsu, Yun L Ma, Sin J Cheng, Shau Y Liu, Eminy H Y Lee
The methyl-CpG-binding protein 2 (MeCP2) gene, MECP2, is an X-linked gene encoding the MeCP2 protein, and mutations of MECP2 cause Rett syndrome (RTT). However, the molecular mechanism of MECP2-mutation-caused RTT is less known. Here we find that MeCP2 could be SUMO-modified by the E3 ligase PIAS1 at Lys-412. MeCP2 phosphorylation (at Ser-421 and Thr-308) facilitates MeCP2 SUMOylation, and MeCP2 SUMOylation is induced by NMDA, IGF-1 and CRF in the rat brain. MeCP2 SUMOylation releases CREB from the repressor complex and enhances Bdnf mRNA expression...
2016: Nature Communications
Andrei N Mardaryev, Bo Liu, Valentina Rapisarda, Krzysztof Poterlowicz, Igor Malashchuk, Jana Rudolf, Andrey A Sharov, Colin A Jahoda, Michael Y Fessing, Salvador A Benitah, Guo-Liang Xu, Vladimir A Botchkarev
During development, multipotent progenitor cells establish lineage-specific programmers of gene activation and silencing underlying their differentiation into specialized cell types. We show that the Polycomb component Cbx4 serves as a critical determinant that maintains the epithelial identity in the developing epidermis by repressing nonepidermal gene expression programs. Cbx4 ablation in mice results in a marked decrease of the epidermal thickness and keratinocyte (KC) proliferation associated with activation of numerous neuronal genes and genes encoding cyclin-dependent kinase inhibitors (p16/p19 and p57)...
January 4, 2016: Journal of Cell Biology
Joshua D Bernstock, Yang-ja Lee, Luca Peruzzotti-Jametti, Noel Southall, Kory R Johnson, Dragan Maric, Giulio Volpe, Jennifer Kouznetsova, Wei Zheng, Stefano Pluchino, John M Hallenbeck
The conjugation/de-conjugation of Small Ubiquitin-like Modifier (SUMO) has been shown to be associated with a diverse set of physiologic/pathologic conditions. The clinical significance and ostensible therapeutic utility offered via the selective control of the global SUMOylation process has become readily apparent in ischemic pathophysiology. Herein, we describe the development of a novel quantitative high-throughput screening (qHTS) system designed to identify small molecules capable of increasing SUMOylation via the regulation/inhibition of members of the microRNA (miRNA)-182 family...
February 2016: Journal of Cerebral Blood Flow and Metabolism
Kyoung-in Cho, Victoria Haney, Dosuk Yoon, Yin Hao, Paulo A Ferreira
Morphological disintegration of neurons is coupled invariably to neural death. In particular, disruption of outer segments of photoreceptor neurons triggers photoreceptor death regardless of the pathological stressors. We show that Ranbp2(-/-)::Tg-Ranbp2(CLDm-HA) mice with mutations in SUMO-binding motif (SBM) of cyclophilin-like domain (CLD) of Ran-binding protein 2 (Ranbp2) expressed in a null Ranbp2 background lack untoward effects in photoreceptors in the absence of light-stress. However, compared to wild type photoreceptors, light-stress elicits profound disintegration of outer segments of Ranbp2(-/-)::Tg-Ranbp2(CLDm-HA) with paradoxical age-dependent resistance of photoreceptors to death and genotype-independent activation of caspases...
December 21, 2015: FEBS Letters
Ji-Hee Choi, Ji-Young Park, Seung Pyo Park, Hyojin Lee, Seulki Han, Kyung Hee Park, Young Ho Suh
SUMOylation is a post-translational modification by which Small Ubiquitin-like MOdifier (SUMO) proteins are covalently linked to the lysine residues of target proteins via an enzymatic cascade. SUMOylation at the synapse plays an important regulatory role in a wide variety of neuronal function such as synapse formation and receptor endocytosis. The metabotropic glutamate receptor type 7 (mGluR7), a presynaptic G protein-coupled receptor, modulates excitatory neurotransmission and synaptic plasticity by inhibiting neurotransmitter release...
March 2016: Neuropharmacology
Audrey Dangoumau, Sylviane Marouillat, Julien Burlaud Gaillard, Rustem Uzbekov, Charlotte Veyrat-Durebex, Hélène Blasco, Christophe Arnoult, Philippe Corcia, Christian R Andres, Patrick Vourc'h
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective death of motor neurons. Mutations in the SOD1 gene encoding the superoxide dismutase 1 are present in 15% of familial ALS cases and in 2% of sporadic cases. These mutations are associated with the formation of SOD1-positive aggregates. The mechanisms of aggregation remain unknown, but posttranslational modifications of SOD1 may be involved. Here, we report that NSC-34 motor neuronal cells expressing mutant SOD1 contained aggregates positive for small ubiquitin modifier-1 (SUMO-1), and in parallel a reduced level of free SUMO-1...
2016: Neuro-degenerative Diseases
Qingxin Cao, Wuguang Lu, Xueting Cai, Chunping Hu, Chen Wang, Juan Ye, Huaijiang Yan, Yang Yang, Zhigang Wang, Jiege Huo, Yan Liu, Ye Yu, Changquan Ling, Peng Cao
OBJECTIVES: To identify an efficient in vitro refolding method to generate highly active His6-tagged scorpion toxin antitumor-analgesic peptide (AGAP) isolated from Escherichia coli inclusion bodies. RESULTS: N- and C-Terminal His6-tagged recombinant (r) AGAP (NHis6-rAGAP and CHis6-rAGAP, respectively) were expressed in E. coli; the purification and refolding conditions were optimized. CHis6-rAGAP, but not NHis6-rAGAP, exhibited significant in vitro antihepatoma activity that was much greater than that of rAGAP produced using SUMO fusion technology (IC50, 0...
December 2015: Biotechnology Letters
Bettina Drisaldi, Luca Colnaghi, Luana Fioriti, Nishta Rao, Cory Myers, Anna M Snyder, Daniel J Metzger, Jenna Tarasoff, Edward Konstantinov, Paul E Fraser, James L Manley, Eric R Kandel
Protein synthesis is crucial for the maintenance of long-term-memory-related synaptic plasticity. The prion-like cytoplasmic polyadenylation element-binding protein 3 (CPEB3) regulates the translation of several mRNAs important for long-term synaptic plasticity in the hippocampus. Here, we provide evidence that the prion-like aggregation and activity of CPEB3 is controlled by SUMOylation. In the basal state, CPEB3 is a repressor and is soluble. Under these circumstances, CPEB3 is SUMOylated in hippocampal neurons both in vitro and in vivo...
June 23, 2015: Cell Reports
Małgorzata H Hall, Adriana Magalska, Monika Malinowska, Błażej Ruszczycki, Iwona Czaban, Satyam Patel, Magdalena Ambrożek-Latecka, Ewa Zołocińska, Hanna Broszkiewicz, Kamil Parobczak, Rajeevkumar R Nair, Marcin Rylski, Robert Pawlak, Clive R Bramham, Grzegorz M Wilczyński
PML is a tumor suppressor protein involved in the pathogenesis of promyelocytic leukemia. In non-neuronal cells, PML is a principal component of characteristic nuclear bodies. In the brain, PML has been implicated in the control of embryonic neurogenesis, and in certain physiological and pathological phenomena in the adult brain. Yet, the cellular and subcellular localization of the PML protein in the brain, including its presence in the nuclear bodies, has not been investigated comprehensively. Because the formation of PML bodies appears to be a key aspect in the function of the PML protein, we investigated the presence of these structures and their anatomical distribution, throughout the adult mouse brain...
June 2016: Brain Structure & Function
Jeremy C McIntyre, Ariell M Joiner, Lian Zhang, Jorge Iñiguez-Lluhí, Jeffrey R Martens
Cilia are evolutionarily conserved organelles found on many mammalian cell types, including neuronal populations. Although neuronal cilia, including those on olfactory sensory neurons (OSNs), are often delineated by localization of adenylyl cyclase 3 (AC3, also known as ADCY3), the mechanisms responsible for targeting integral membrane proteins are largely unknown. Post-translational modification by small ubiquitin-like modifier (SUMO) proteins plays an important role in protein localization processes such as nuclear-cytosolic transport...
May 15, 2015: Journal of Cell Science
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