RESUMO
Since the discovery of SUMOs (small ubiquitin-like modifiers) over 20 years ago, sumoylation has recently emerged as an important posttranslational modification involved in almost all aspects of cellular physiology. In neurons, sumoylation dynamically modulates protein function and consequently plays an important role in neuronal maturation, synapse formation and plasticity. Thus, the dysfunction of sumoylation pathway is associated with many different neurological disorders. Hundreds of different proteins implicated in the pathogenesis of neurological disorders are SUMO-modified, indicating the importance of sumoylation involved in the neurological diseases. In this review, we summarize the growing findings on protein sumoylation in neuronal function and dysfunction. It is essential to have a thorough understanding on the mechanism how sumoylation contributes to neurological diseases in developing efficient therapy for these diseases.
Assuntos
Doenças do Sistema Nervoso/genética , Neurogênese/genética , Processamento de Proteína Pós-Traducional/genética , Sumoilação/genética , Humanos , Doenças do Sistema Nervoso/fisiopatologia , Neurônios/metabolismo , Neurônios/patologia , Ubiquitina/genéticaRESUMO
Sumoylation, a post-translational modification discovered over a decade ago, turns out to be a very important regulatory mechanism mediating multiple cellular processes. Recent studies from our laboratory and others also revealed that it plays a crucial role in regulating both differentiation and pathogenesis of the ocular lens. This review will summarize these progresses.
Assuntos
Catarata/genética , Diferenciação Celular/genética , Processamento de Proteína Pós-Traducional/genética , Sumoilação/genética , Catarata/fisiopatologia , Humanos , Cristalino/patologiaRESUMO
PURPOSE: The protein phosphatase-2A (PP-2A) is one of the most important serine/threonine phosphatases in eukaryotes. The holoenzyme of PP-2A consists of three subunits: a scaffold A subunit, a catalytic C subunit and a regulatory B subunit. While both A and C subunits are coded by two different genes, the B subunits exist in 26 or more isoforms which are encoded by at least 15 different genes. Previous studies have shown that besides regulating specific PP-2A activity, various B subunits may have other functions. To explore the possible roles of the regulatory subunits of PP-2A in vertebrate development, we have cloned the gene encoding goldfish striatin, a member of the B'" family regulatory subunits for PP-2A, and determined their tissue-specific and temporal expression patterns. METHODS: The cDNA cloning was conducted with RT-PCR-based RACE. The mRNA expression levels for the goldfish striatin were analyzed with RT-PCR. The expression levels of the striatin protein from goldfish were determined with Western blot analysis. The semi-quantitation of the mRNA and protein expression levels was conducted with the software of U-scanning. RESULTS: Our study revealed that the full length cDNA for striatin consists of 2965 bp coding for a deduced protein of 769 amino acids, which bears a very high level of amino acid sequence identity with the homolog protein from other species. The striatin mRNA is highly expressed in the kidney, to a less degree in brain, fin, muscle, liver, ovary and gill, and the lowest in testis and heart. Similar pattern of protein expression is detected in the above 9 tissues. During the development of goldfish, the striatin mRNA maintains a relatively high level at the 2-cell, multiple cell and blastula stages. Then, it drops down substantially at gastrula stage and fluctuates around this level in the next 8 different stages. At the protein level, the striatin maintained higher level from 2-cell to gastrula stages, then decreased at neurula and optic vesicle stages, and gradually increased again to peak at eye pigmentation stage, then slightly decreased in the next few stages of development. CONCLUSIONS: Our results suggest that the striatin may play an important role in regulating goldfish development and adult tissue homeostasis. While the former function may or may not occur through PP- 2A functions, the later function appears to occur via PP-2A activity.
Assuntos
Proteínas de Ligação a Calmodulina/genética , Carpa Dourada/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Fosfoproteínas Fosfatases/genética , Proteína Fosfatase 2/genética , Sequência de Aminoácidos/genética , Animais , Domínio Catalítico/genética , Clonagem Molecular , Regulação da Expressão Gênica no Desenvolvimento/genética , Carpa Dourada/crescimento & desenvolvimento , Humanos , Subunidades Proteicas/genética , Homologia de Sequência de AminoácidosRESUMO
CREB is an ubiquitous transcription factor regulating diverse cellular responses. Its phosphorylation at S133 is an essential event for its activation in both nervous and visual systems. The activated CREB is implicated in the regulation of development, protection, learning, memory and plasticity in the nerve system. Moreover, sumoylation, an important post-translational modification of protein, plays a key role in sustaining CREB activation in the rat hippocampus in order to enhance the long-term memory and other aspects. In the visual system, although the CREB activation by phosphorylation at S133 is similar to that as observed in the nervous system, the role of CREB sumoylation remains to be explored. This review will discuss the aspects of CREB functions and their regulation by phosphorylation and sumoylation in both systems.
Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Memória/fisiologia , Sumoilação/genética , Visão Ocular/genética , Animais , Regulação da Expressão Gênica , Hipocampo/crescimento & desenvolvimento , Hipocampo/fisiologia , Humanos , Fenômenos Fisiológicos do Sistema Nervoso/genética , Fosforilação/genética , Processamento de Proteína Pós-Traducional/genética , Ratos , Transdução de Sinais/genética , Visão Ocular/fisiologiaRESUMO
The protein serine/threonine phosphatases-1 and -2A are major cellular phosphatases, playing a fundamental role in organisms from prokaryotes to eukaryotes. They contribute to 90% dephosphorylation in eukaryote proteins. In the eye, both phosphatases are highly expressed and display important functions in regulating normal eye development. Moreover, they are implicated in pathogenesis through modulation of stress-induced apoptosis. Here we review the recent progresses on these aspects.
Assuntos
Catarata/genética , Olho/metabolismo , Glaucoma/genética , Proteína Fosfatase 1/genética , Proteína Fosfatase 2/genética , Subunidades Proteicas/genética , Animais , Apoptose , Catarata/enzimologia , Catarata/patologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Olho/crescimento & desenvolvimento , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Glaucoma/enzimologia , Glaucoma/patologia , Carpa Dourada , Fatores de Transcrição de Choque Térmico , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Organogênese/genética , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados/genética , Fatores de Transcrição Box Pareados/metabolismo , Proteína Fosfatase 1/metabolismo , Proteína Fosfatase 2/metabolismo , Subunidades Proteicas/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
In this study, we evaluated the effect and possible mech-anism of action of dietary conjugated linoleic acid (CLA) on pig body fat deposition. Landrace piglets (N = 48) were randomly divided into three groups, which were fed diets containing 0% (control), 1%, or 2% CLA. Dorsal and abdominal subcutaneous adipose tissues were col-lected, and real-time polymerase chain reaction (PCR) was used to de-termine the expression of adipocyte differentiation marker genes and associated microRNAs (miRNAs). Our results indicated that dietary CLA significantly decreased body fat deposition in the pig dorsum. The expression of adipocyte differentiation marker genes, including peroxi-some proliferator-activated receptor (PPAR)-γ and CCAAT/enhancer-binding protein α (C/EBPα) were not affected, whereas the expression of fatty acid binding protein 4 (FABP4) was significantly enhanced (P < 0.05). The expression of miR-27 and miR-143 in adipose tissue was significantly decreased. Data analysis indicated a significant negative correlation between miR-27 and FABP4 expression in the dorsal sub-cutaneous adipose tissue. In addition, the expression of miR-143 and miR-27 exhibited a significant negative relationship with FABP4 and PPARγ in the abdominal subcutaneous adipose tissue. Thus, miRNA levels in adipose tissues could be modulated by CLA, thereby affecting adipose metabolism.
Assuntos
Tecido Adiposo/efeitos dos fármacos , Ração Animal/análise , Suplementos Nutricionais , Proteínas de Ligação a Ácido Graxo/genética , Ácidos Linoleicos Conjugados/administração & dosagem , MicroRNAs/genética , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Animais , Distribuição da Gordura Corporal , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Proteínas de Ligação a Ácido Graxo/agonistas , Proteínas de Ligação a Ácido Graxo/metabolismo , Regulação da Expressão Gênica , Metabolismo dos Lipídeos/efeitos dos fármacos , MicroRNAs/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , SuínosRESUMO
A total of 160 Rongchang pigs (26.76±1.78 kg) were randomly assigned to 5 dietary treatment groups until their body weight (BW) reached 90 kg. The diets were supplemented with 0, 0.5, 1.0, 1.5, and 2.0% conjugated linoleic acid (CLA). Our results showed that the 1.0 to 2.0% CLA-fed pigs had less back fat deposition when their BW reached 90 kg than the pigs that received less than 1% CLA. During the 30 to 60 kg growing period, 1.0, 1.5, and 2.0% CLA treatments improved pork quality by significantly reducing the pork pH (P<0.01) and color value (P<0.05), but they increased marble scaling (P<0.01). Similarly, the 1.5 and 2.0% CLA-fed pigs had more marble than other pigs when their BW reached 90 kg. Furthermore, CLA significantly affected the expression of muscle fiber-type genes. The 1.5% CLA-fed pigs exhibited the highest mRNA expression of MyHC1 and MyHC2a (P<0.05) at 60 kg BW. At 90 kg BW, the highest expression of MyHC1 and MyHC2a (P<0.05) was found in the 2.0% CLA group. However, MyHC2x was downregulated in the CLA-fed pigs at this time. In addition, CLA supplements did not evidently alter mRNA expression of MyHC2b at all times. These results demonstrate that CLA could affect carcass traits and improve the meat quality of growing-finishing pigs by altering the expression of genes related to muscle growth and development; 1-1.5% CLA was the most appropriate CLA dose.
