Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 22
Filter
1.
Chinese Medical Journal ; (24): 1349-1357, 2023.
Article in English | WPRIM | ID: wpr-980848

ABSTRACT

BACKGROUND@#Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown.@*METHODS@#Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements.@*RESULTS@#Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R.@*CONCLUSION@#PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.


Subject(s)
Rats , Male , Animals , Myocardial Reperfusion Injury/metabolism , Connexin 43/genetics , Sumoylation , Down-Regulation , Rats, Sprague-Dawley , Arrhythmias, Cardiac/drug therapy , Myocardial Ischemia/metabolism , RNA, Small Interfering/metabolism
2.
Chinese Journal of Oncology ; (12): 1362-1368, 2022.
Article in Chinese | WPRIM | ID: wpr-969796

ABSTRACT

Objective: To inhibit the stemness maintenance potential of endometrial cancer and increase the sensitivity of endometrial cancer side population cells to chemotherapy drugs by inducing extensive deSUMOylation modification of proteins. Methods: Flow cytometry was used to sort and culture CD133(+) CD44(+) KLE endometrial cancer cell clone spheres. Protein expression level of small ubiquitin-related modifier 1 (SUMO1) and two stemness maintenance genes of tumor side population cells, octamer binding transcription factor-4 (Oct4) and sex determining region Y-box2 (Sox2), were detected by western blotting method. Lentivirus-mediated Sentrin/SUMO-specific proteases 1 (SENP1) gene was stably transfected into KLE side population cells. Western blotting was used to detect the protein expressions of SENP1, SUMO1, Oct4 and Sox2. The clone formation rate was compared between KLE side population cells with or without SENP1 overexpression. Flow cytometry was applied to detect cell cycle changes. 3-(4, 5-Dimethylthiazole-2)-2, 5-diphenyl-tetrazolium bromide (MTT) experiment and flow cytometry apoptosis method were used to detect the chemosensitivity of the side population of endometrial cancer cells to cisplatin. Tumor-bearing mouse models of endometrial cancer were established to detect the effect of SENP1 overexpression on the chemotherapy sensitivity of cisplatin. Results: Compared with CD133(-)CD44(-) KLE cells, CD133(+) CD44(+) KLE side population cells could form clonal spheres and express higher levels of SUMO1, Oct4 and Sox2 proteins (P<0.05). Compared with KLE side population cells that were not transfected with SENP1 gene, the expression level of SENP1 protein in KLE side population cells overexpressing SUMO1、Oct4 and Sox2 were lower. The clonal sphere formation rate was reduced from (25.67±5.44)% to (7.46±1.42)%, and cell cycle shifted from G(0)/G(1) phase to G(2) phase. IC(50) of cisplatin decreased from (55.46±6.14) μg/ml to (11.55±3.12) μg/ml, and cell apoptosis rate increased from (9.76±2.09)% to (16.79±3.44)%. Overexpression of SENP1 could reduce the tumorigenesis rate of KLE side population cells in vivo and increase their chemotherapy sensitivity to cisplatin (P<0.05). Conclusion: Overexpression of SENP1 can induce protein deSUMOylation modification, inhibit the stemness maintenance potential of endometrial cancer side population cells, and enhance their chemotherapy sensitivity, which provides a new reference for gene therapy of endometrial cancer.


Subject(s)
Animals , Female , Humans , Mice , Apoptosis , Cell Line, Tumor , Cisplatin/pharmacology , Cysteine Endopeptidases/metabolism , Endometrial Neoplasms/genetics , Side-Population Cells/pathology , Sumoylation
3.
Chinese Medical Journal ; (24): 466-473, 2019.
Article in English | WPRIM | ID: wpr-774826

ABSTRACT

OBJECTIVE@#Small ubiquitin-related modifiers (SUMOs) are a group of post-translational modification proteins extensively expressed in eukaryotes. Abnormal SUMOylation can lead to the development of various diseases. This article summarizes the progress on research of the role of SUMOs in various types of kidney diseases to further increase the understanding of the regulatory functions of SUMOylation in the pathogenesis of kidney diseases.@*DATA SOURCES@#This review was based on articles published in the PubMed databases up to January 2018, using the keywords including "SUMOs," "SUMOylation," and "kidney diseases."@*STUDY SELECTION@#Original articles and critical reviews about SUMOs and kidney disease were selected for this review. A total of 50 studies were in English.@*RESULTS@#SUMO participates in the activation of NF-κB inflammatory signaling pathway, playing a central regulatory role in the inflammation and progression of DN, and the secretion of various chemokines in AKI. SUMO involves in the regulation of TG2 and Nrf2 antioxidant stress, affecting renal tubular injury in AKI. SUMO affects the MAPK/ERK pathway, regulating intracellular signal transduction, modulating the transcription and expression of effector molecules in DN. SUMO contributes to the TGF-β/Smad pathway, leading to fibrosis of the kidney. The conjugate combination of SUMO and p53 regulates cell proliferation and apoptosis, and participates in the regulation of tumorigenesis. In addition, SUMOylation of MITF modulates renal tumors secondary to melanoma, Similarly, SUMOylation of tumor suppressor gene VHL regulates the occurrence of renal cell carcinoma in VHL syndrome.@*CONCLUSIONS@#Tissue injury, inflammatory responses, fibrosis, apoptosis, and tumor proliferation in kidney diseases all involve SUMOs. Further research of the substrate SUMOylation and regulatory mechanisms of SUMO in kidney diseases will improve and develop new treatment measures and strategies targeting kidney diseases.


Subject(s)
Humans , Acute Kidney Injury , Carcinoma, Renal Cell , Diabetic Nephropathies , Fibrosis , Kidney , Pathology , Kidney Diseases , Metabolism , Kidney Neoplasms , SUMO-1 Protein , Physiology , Sumoylation
4.
Acta Academiae Medicinae Sinicae ; (6): 419-424, 2019.
Article in Chinese | WPRIM | ID: wpr-776016

ABSTRACT

The chromosomal aneuploidy in oocytes is one of main causes of abortion and neonatal birth defects.It is mainly due to the premature separation of sister chromatid caused by the loss of Cohesin protein complex and the non-disjunction sister chromatids caused by abnormal microtubule dynamics aneuploidy.As a pathway of protein post-translational modification,SUMO modification(or SUMOylation)involves many physiological regulation processes including cell proliferation,differentiation,apoptosis,and cycle regulation.In the oocytes,SUMOylation can regulate the localization of Cohesin protein complex on the chromosome to affect the chromosomal aneuploidy in oocytes caused by premature separation of sister chromatid.On the other hand,SUMOylation can regulate the microtubule dynamics to affect the chromosomal aneuploidy in oocytes caused by non-disjunction sister chromatids.Therefore,SUMOylation plays an important role in regulating the chromosomal aneuploidy of oocytes;the exact mechanisms via which the SUMOylated substrates affect aneuploidy in oocytes remain unclear.This articles reviews the roles of SUMOylation in premature separation and non-isolated chromatid aneuploidy in oocyte from the effects of SUMOylationon Cohesin protein complex and microtubule dynamics.


Subject(s)
Humans , Aneuploidy , Cell Cycle Proteins , Chromatids , Chromosomal Proteins, Non-Histone , Chromosome Segregation , Microtubules , Oocytes , Cell Biology , Sumoylation
5.
Experimental & Molecular Medicine ; : e427-2018.
Article in English | WPRIM | ID: wpr-739498

ABSTRACT

Sumoylation, the conjugation of a small ubiquitin-like modifier (SUMO) protein to a target, has diverse cellular effects. However, the functional roles of the SUMO modification during myogenesis have not been fully elucidated. Here, we report that basal sumoylation of histone deacetylase 1 (HDAC1) enhances the deacetylation of MyoD in undifferentiated myoblasts, whereas further sumoylation of HDAC1 contributes to switching its binding partners from MyoD to Rb to induce myocyte differentiation. Differentiation in C2C12 skeletal myoblasts induced new immunoblot bands above HDAC1 that were gradually enhanced during differentiation. Using SUMO inhibitors and sumoylation assays, we showed that the upper band was caused by sumoylation of HDAC1 during differentiation. Basal deacetylase activity was not altered in the SUMO modification-resistant mutant HDAC1 K444/476R (HDAC1 2R). Either differentiation or transfection of SUMO1 increased HDAC1 activity that was attenuated in HDAC1 2R. Furthermore, HDAC1 2R failed to deacetylate MyoD. Binding of HDAC1 to MyoD was attenuated by K444/476R. Binding of HDAC1 to MyoD was gradually reduced after 2 days of differentiation. Transfection of SUMO1 induced dissociation of HDAC1 from MyoD but potentiated its binding to Rb. SUMO1 transfection further attenuated HDAC1-induced inhibition of muscle creatine kinase luciferase activity that was reversed in HDAC1 2R. HDAC1 2R failed to inhibit myogenesis and muscle gene expression. In conclusion, HDAC1 sumoylation plays a dual role in MyoD signaling: enhancement of HDAC1 deacetylation of MyoD in the basally sumoylated state of undifferentiated myoblasts and dissociation of HDAC1 from MyoD during myogenesis.


Subject(s)
Creatine Kinase, MM Form , Gene Expression , Histone Deacetylase 1 , Histone Deacetylases , Histones , Luciferases , Muscle Cells , Muscle Development , Myoblasts , Myoblasts, Skeletal , Sumoylation , Transfection
6.
Chinese Journal of Contemporary Pediatrics ; (12): 403-409, 2018.
Article in Chinese | WPRIM | ID: wpr-689617

ABSTRACT

<p><b>OBJECTIVE</b>To study the expression of SUMO-modified CCAAT enhancer binding protein α (C/EBPα) in preterm rat model of bronchopulmonary dysplasisa (BPD) induced by hyperoxia exposure and its role.</p><p><b>METHODS</b>Eighteen preterm rats were randomly divided into an air group and a hyperoxia group (n=9 each). The model of BPD was prepared in preterm rats exposed to hyperoxia. The rats from the two groups were sacrificed on postnatal days 4, 7 and 14 respectively (3 rats at each time) and lung tissues were harvested. Periodic acid-Schiff (PAS) staining was used to observe the differentiation of rat lung tissues. Ki67 expression was detected by immunohistochemistry. Western blot was used to measure the protein expression of small ubiquitin-related modifier-1(SUMO1) and C/EBPα. A co-immunoprecipitation assay was performed to measure the protein expression of SUMO-modified C/EBPα.</p><p><b>RESULTS</b>Compared with the air group, the hyperoxia group showed a decreased glycogen content in the lung tissue on postnatal day 4, and an increased content on postnatal days 7 and 14. Over the time of hyperoxia exposure, the hyperoxia group showed an increased expression of Ki67 in the lung tissue compared with the air group at all time points. Compared with the air group, the protein expression of C/EBPα increased on postnatal day 4 and decreased on postnatal days 7 and 14 in the hyperoxia group (P<0.05). The hyperoxia group had significantly upregulated expression of SUMO1 and SUMO-modified C/EBPα compared with the air group at all time points (P<0.05). In the hyperoxia group, the protein expression of SUMO-modified C/EBPα was positively correlated with the glycogen content (r=0.529, P<0.05) and the expression of Ki67 (r=0.671, P<0.05).</p><p><b>CONCLUSIONS</b>Hyperoxia may induce over-proliferation and differentiation disorders of alveolar epithelial cells in preterm rat model of BPD, possibly through an increased expression of SUMO-modified C/EBP&alpha.</p>


Subject(s)
Animals , Rats , Animals, Newborn , Bronchopulmonary Dysplasia , Metabolism , Pathology , CCAAT-Enhancer-Binding Protein-alpha , Metabolism , Cell Proliferation , Disease Models, Animal , Hyperoxia , Pathology , Ki-67 Antigen , Pulmonary Alveoli , Pathology , Rats, Sprague-Dawley , Sumoylation
7.
Protein & Cell ; (12): 63-77, 2016.
Article in English | WPRIM | ID: wpr-757168

ABSTRACT

SUMOylation is recently found to function as a targeting signal for the degradation of substrates through the ubiquitin-proteasome system. RNF4 is the most studied human SUMO-targeted ubiquitin E3 ligase. However, the relationship between SUMO proteases, SENPs, and RNF4 remains obscure. There are limited examples of the SENP regulation of SUMO2/3-targeted proteolysis mediated by RNF4. The present study investigated the role of SENP3 in the global protein turnover related to SUMO2/3-targeted ubiquitination and focused in particular on the SENP3 regulation of the stability of Sp1. Our data demonstrated that SENP3 impaired the global ubiquitination profile and promoted the accumulation of many proteins. Sp1, a cancer-associated transcription factor, was among these proteins. SENP3 increased the level of Sp1 protein via antagonizing the SUMO2/3-targeted ubiquitination and the consequent proteasome-dependent degradation that was mediated by RNF4. De-conjugation of SUMO2/3 by SENP3 attenuated the interaction of Sp1 with RNF4. In gastric cancer cell lines and specimens derived from patients and nude mice, the level of Sp1 was generally increased in parallel to the level of SENP3. These results provided a new explanation for the enrichment of the Sp1 protein in various cancers, and revealed a regulation of SUMO2/3 conjugated proteins whose levels may be tightly controlled by SENP3 and RNF4.


Subject(s)
Animals , Humans , Mice , Cysteine Endopeptidases , Genetics , Metabolism , Gene Expression Regulation, Neoplastic , Immunoenzyme Techniques , Immunoprecipitation , Mice, Inbred BALB C , Mice, Nude , Prognosis , Protein Processing, Post-Translational , Proteolysis , RNA, Messenger , Genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Small Ubiquitin-Related Modifier Proteins , Genetics , Metabolism , Sp1 Transcription Factor , Genetics , Metabolism , Stomach Neoplasms , Genetics , Metabolism , Pathology , Sumoylation , Tumor Cells, Cultured , Ubiquitination , Ubiquitins , Genetics , Metabolism , Xenograft Model Antitumor Assays
8.
Acta Physiologica Sinica ; (6): 435-454, 2016.
Article in English | WPRIM | ID: wpr-331641

ABSTRACT

Estrogen receptor (ER) and progesterone receptor (PR) are two important members of steroid receptors family, an evolutionarily conserved family of transcription factors. Upon binding to their ligands, ER and PR enter cell nucleus to interact with specific DNA element in the context of chromatin to initiate the transcription of diverse target genes, which largely depends on the timely recruitment of a wide range of cofactors. Moreover, the interactions between steroid hormones and their respective receptors also trigger post-translational modifications on these receptors to fine-tune their transcriptional activities. Besides the well-known phosphorylation modifications on tyrosine and serine/threonine residues, recent studies have identified several other covalent modifications, such as ubiquitylation and sumoylation. These post-translational modifications of steroid receptors affect its stability, subcellular localization, and/or cofactor recruitment; eventually influence the duration and extent of transcriptional activation. This review is to focus on the recent research progress on the transcriptional activation of nuclear ER and PR as well as their physiological functions in early pregnancy, which may help us to better understand related female reproductive diseases.


Subject(s)
Ligands , Phosphorylation , Receptors, Estrogen , Receptors, Progesterone , Sumoylation , Transcriptional Activation
9.
Journal of Biomedical Engineering ; (6): 1380-1384, 2015.
Article in Chinese | WPRIM | ID: wpr-357863

ABSTRACT

PNAS-4 is a novel pro-apoptosis gene identified latetly. In recent years, there has been a large number of research reports on the basic studies about PNAS-4 in cancer gene therapy and gene therapy of PNAS-4 alone or combined with chemotherapy or radiotherapy manifested a good application prospect, but its molecular mechanisms to promote apoptosis is not clear yet. In this paper, recent research about PNAS-4 in cancer gene therapy is briefly reviewed, and recent hypotheses on its molecular mechanisms to promote apoptosis are especially elucidated. Based on its newly identified characteristics of structural domain, we made a point that PNAS-4 might regulate functions of some target protein related to apoptosis by deSumoylation as a new deSumoylating isopeptidase, and consequently promote apoptosis.


Subject(s)
Humans , Apoptosis , Apoptosis Regulatory Proteins , Genetics , Genetic Therapy , Neoplasms , Therapeutics , Sumoylation
10.
Chinese Journal of Virology ; (6): 560-564, 2015.
Article in Chinese | WPRIM | ID: wpr-296247

ABSTRACT

The influenza virus has evolved numerous mechanisms to overcome host defenses for its benefit. It can also manipulate the immune system to stop it monitoring and clearing the virus. Small ubiquitin-like modifier (SUMO)ylation is emerging as a key post-translational modification that plays an important part in virus replication. This brief review focuses on recent findings on the roles of SUMOylation during infection by the influenza virus. As such, it will aid understanding of the mechanism of action of infection by the influenza virus, and help to provide new strategies for anti-viral treatment.


Subject(s)
Animals , Humans , Influenza, Human , Virology , Orthomyxoviridae , Genetics , Metabolism , Sumoylation , Viral Proteins , Genetics , Metabolism , Virus Replication
11.
Endocrinology and Metabolism ; : 381-388, 2015.
Article in English | WPRIM | ID: wpr-153717

ABSTRACT

BACKGROUND: Hes6 is a transcriptional regulator that induces transcriptional activation by binding to transcription repressor Hes1 and suppressing its activity. Hes6 is controlled by the ubiquitin-proteosome-mediated degradation system. Here we investigated the sumoylation of Hes6 and its functional role in its rhythmic expression. METHODS: Hes6, SUMO, and ubiquitin were transfected into HeLa cells and the expression pattern was observed by Western blot and immunoprecipitation. To confirm the effect of sumoylation on the rhythmic expression of Hes6, we generated mouse Hes6 promoter-driven GFP-Hes6 fusion constructs and expressed these constructs in NIH 3T3 cells. RESULTS: Overexpression of SUMO led to sumoylation of Hes6 at both lysine 27 and 30. Protein stability of Hes6 was decreased by sumoylation. Moreover, expression of a Hes6 sumoylation-defective mutant, the 2KR (K27/30R) mutant, or co-expression of SUMO protease SUSP1 with native Hes6, strongly reduced ubiquitination. In addition, sumoylation was associated with both the rhythmic expression and transcriptional regulation of Hes6. Wild type Hes6 showed oscillatory expression with about 2-hour periodicity, whereas the 2KR mutant displayed a longer period. Furthermore, sumoylation of Hes6 derepressed Hes1-induced transcriptional repression. CONCLUSION: Hes6 sumoylation plays an important role in the regulation of its stability and Hes1-mediated transcription. These results suggest that sumoylation may be crucial for rhythmic expression of Hes6 and downstream target genes.


Subject(s)
Animals , Humans , Mice , Blotting, Western , HeLa Cells , Immunoprecipitation , Lysine , NIH 3T3 Cells , Periodicity , Protein Stability , Proteolysis , Repression, Psychology , Sumoylation , Transcriptional Activation , Ubiquitin , Ubiquitination
12.
Immune Network ; : 321-327, 2014.
Article in English | WPRIM | ID: wpr-116963

ABSTRACT

TGF-beta induces IgA class switching by B cells. We previously reported that Smad3 and Smad4, pivotal TGF-beta signal-transducing transcription factors, mediate germline (GL) alpha transcription induced by TGF-beta1, resulting in IgA switching by mouse B cells. Post-translational sumoylation of Smad3 and Smad4 regulates TGF-beta-induced transcriptional activation in certain cell types. In the present study, we investigated the effect of sumoylation on TGF-beta1-induced, Smad3/4-mediated GLalpha transcription and IgA switching by mouse B cell line, CH12F3-2A. Overexpression of small ubiquitin-like modifier (SUMO)-1, SUMO-2 or SUMO-3 did not affect TGF-beta1-induced, Smad3/4-mediated GLalpha promoter activity, expression of endogenous GLalpha transcripts, surface IgA expression, and IgA production. Next, we tested the effect of the E3 ligase PIASy on TGF-beta1-induced, Smad3/4-mediated GLalpha promoter activity. We found that PIASy overexpression suppresses the GLalpha promoter activity in cooperation with histone deacetylase 1. Taken together, these results suggest that SUMO itself does not affect regulation of GLalpha transcription and IgA switching induced by TGF-beta1/Smad3/4, while PIASy acts as a repressor.


Subject(s)
Animals , Mice , B-Lymphocytes , Cell Line , Histone Deacetylase 1 , Immunoglobulin A , Immunoglobulin Class Switching , Small Ubiquitin-Related Modifier Proteins , SUMO-1 Protein , Sumoylation , Transcription Factors , Transcriptional Activation , Transforming Growth Factor beta , Transforming Growth Factor beta1 , Ubiquitin-Protein Ligases
13.
Protein & Cell ; (12): 62-70, 2013.
Article in English | WPRIM | ID: wpr-757833

ABSTRACT

The paracaspase MALT1 is essential for the activation of NF-κB in response to T cell receptor (TCR) stimulation. It recruits downstream TRAF6 and activates the E3 ligase activity of TRAF6 to polyubiquitinate several targets, which ultimately leads to NF-κB activation. Here we identified ubiquitin-specific protease 2a (USP2a) as a MALT1-associated protein by biochemical affinity purification. Endogenous USP2a constitutively interacted with TRAF6, but dynamically interacted with MALT1 and CARMA1 in a stimulation-dependent manner. RNA interference (RNAi)-mediated silencing of USP2a attenuated TCR-induced NF-κB activation and production of interleukin-2 (IL-2). In addition, the ubiquitination of MALT1 and TRAF6 were both suppressed by USP2a knockdown. By knockdown and reconstitution assays, we found that USP2a mediated the interaction between MALT1 and TRAF6 in a catalytic activity-dependent manner. Furthermore, USP2a deSUMOylated TRAF6. Our findings implicate that USP2a plays an important role in TCR signaling by deSUMOylating TRAF6 and mediating TRAF6-MALT1 interaction.


Subject(s)
Humans , Caspases , Metabolism , Endopeptidases , Genetics , Metabolism , Gene Knockdown Techniques , HEK293 Cells , Interleukin-2 , Jurkat Cells , Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein , NF-kappa B , Metabolism , Neoplasm Proteins , Metabolism , Receptors, Antigen, T-Cell , Metabolism , Signal Transduction , Sumoylation , TNF Receptor-Associated Factor 6 , Metabolism
14.
Journal of Experimental Hematology ; (6): 218-221, 2013.
Article in Chinese | WPRIM | ID: wpr-325181

ABSTRACT

Small ubiquitin-related modifier (SUMO) can be covalently attached to target proteins and thereby plays a crucial role in regulating the normal functions of cells, such as protein-protein interaction, subcellular localization, DNA repair, cell cycle and transcription factor regulation. Several lines have implicated that sumoylation is important in disease occurrence and development. This brief review will focus on some recent findings about the roles of sumoylation in the etiology and treatment of hematological malignancies.


Subject(s)
Animals , Humans , Hematologic Diseases , Pathology , Therapeutics , Sumoylation
15.
Acta Physiologica Sinica ; (6): 89-95, 2013.
Article in Chinese | WPRIM | ID: wpr-333130

ABSTRACT

Death domain-associated protein (DAXX) as a multifunctional nuclear protein widely resides in nucleolus, nucleoplasm, chromatin, promyelocytic leukaemia nuclear bodies (PML-NBs) and cytoplasm. It plays significant roles in transcriptional regulation, apoptosis, cell cycle and other biological activities. Small ubiquitin-like modifier (SUMO) is required for SUMOylation which is a highly conserved post-translational modification in a wide variety of cellular processes. Numerous studies demonstrated that SUMOylation has a great effect on the subcellular localization and functional regulation of DAXX. This review will provide a summary for SUMOylation of DAXX.


Subject(s)
Humans , Adaptor Proteins, Signal Transducing , Physiology , Gene Expression Regulation , Nuclear Proteins , Physiology , Sumoylation
16.
Acta Physiologica Sinica ; (6): 253-262, 2013.
Article in Chinese | WPRIM | ID: wpr-333108

ABSTRACT

Small ubiquitin-related modifiers (SUMOs) belong to an important class of ubiquitin like proteins. SUMOylation is a post-translational modification process that regulates the functional properties of many proteins, among which are several proteins implicated in neurodegenerative diseases. This study was aimed to investigate the changes of SUMO-1 expression and modification, and the relationship between SUMO-1 and Alzheimer's disease (AD) pathology in APP/PS1 transgenic AD mice. Using Western blot, co-immunoprecipitation and immunofluorescent staining methods, the SUMO-1 expression and modification and its relation to tau, amyloid precursor protein (APP) and β-amyloid protein (Aβ) in the 12-month-old APP/PS1 transgenic AD mice were analyzed. The results showed that: (1) Compared with the normal wild-type mice, the expression and modification of SUMO-1 increased in brain of AD mice, which was accompanied by an increase of ubiquitination; (2) In RIPA soluble protein fraction of cerebral cortex, co-immunoprecipitation analysis showed tau SUMOylated by SUMO-1 increased in AD mice, however, AT8 antibody labeled phosphorylated tau was less SUMOylated whereas PS422 antibody labeled phosphorylated tau was similar to control mice; (3) Double immunofluorescent staining showed that SUMO-1 could distributed in amyloid plaques, appearing that some of SUMO-1 diffused in centre of some plaques and some of SUMO-1 co-localized with AT8 labeled phosphorylated tau forming punctate aggregates around amyloid plaques which was concerned as dystrophic neurites, however, less Aβ, APP and PS422 labeled phosphorylated tau were found co-localized with SUMO-1. These results suggest that SUMO-1 expression and modification increase abnormally in transgenic AD mice, which may participate in modulation of the formation of senile plaques and dystrophic neurites.


Subject(s)
Animals , Mice , Alzheimer Disease , Amyloid beta-Peptides , Metabolism , Amyloid beta-Protein Precursor , Metabolism , Brain , Pathology , Mice, Transgenic , Neurites , Pathology , Phosphorylation , Plaque, Amyloid , SUMO-1 Protein , Metabolism , Sumoylation , tau Proteins , Metabolism
17.
Yonsei Medical Journal ; : 545-559, 2013.
Article in English | WPRIM | ID: wpr-56831

ABSTRACT

Peroxisome proliferator-activated receptor gamma (PPARgamma) belongs to a nuclear receptor superfamily; members of which play key roles in the control of body metabolism principally by acting on adipose tissue. Ligands of PPARgamma, such as thiazolidinediones, are widely used in the treatment of metabolic syndromes and type 2 diabetes mellitus (T2DM). Although these drugs have potential benefits in the treatment of T2DM, they also cause unwanted side effects. Thus, understanding the molecular mechanisms governing the transcriptional activity of PPARgamma is of prime importance in the development of new selective drugs or drugs with fewer side effects. Recent advancements in molecular biology have made it possible to obtain a deeper understanding of the role of PPARgamma in body homeostasis. The transcriptional activity of PPARgamma is subject to regulation either by interacting proteins or by modification of the protein itself. New interacting partners of PPARgamma with new functions are being unveiled. In addition, post-translational modification by various cellular signals contributes to fine-tuning of the transcriptional activities of PPARgamma. In this review, we will summarize recent advancements in our understanding of the post-translational modifications of, and proteins interacting with, PPARgamma, both of which affect its transcriptional activities in relation to adipogenesis.


Subject(s)
Gene Expression Regulation , Homeostasis , Models, Genetic , PPAR gamma/genetics , Protein Processing, Post-Translational , Sumoylation , Transcription Factors/metabolism , Ubiquitination
18.
Chinese Journal of Contemporary Pediatrics ; (12): 800-803, 2012.
Article in Chinese | WPRIM | ID: wpr-353861

ABSTRACT

Gata4 is an important transcription factor in heart development. Gata4 post-transcriptional protein modification regulates transcriptional activity and DNA binding, which in turn affects expression of downstream genes and transcription factors, differentiation of embryonic stem cells and cardiogenesis. This article summarizes the effect of post-transcriptional protein modification on transcriptional activity of Gata4 and the relationship between this effect and congenital heart disease. It was shown that acetylation, phosphorylation and SUMOylation upregulate transcriptional activity, DNA binding, downstream gene expression and embryonic stem cell differentiation. On the other hand, methylation and deacetylation downregulate Gata4 transcriptional activity. Post-transcriptional protein modification of Gata4 is very important in clinical research on congenital and other heart diseases.


Subject(s)
Animals , Humans , Acetylation , GATA4 Transcription Factor , Chemistry , Genetics , Metabolism , Methylation , Phosphorylation , Protein Processing, Post-Translational , Sumoylation
19.
Soonchunhyang Medical Science ; : 95-101, 2012.
Article in Korean | WPRIM | ID: wpr-73336

ABSTRACT

OBJECTIVE: The incidence of colorectal carcinomas continues to rise in Korea due to the westernized life style. However, the precise colorectal carcinogenic mechanisms remain to be elucidated. The protein products of oncogenes and cancer suppressor genes play important roles in the carcinogenesis. The effects of the proteins are influenced by post-translational modifications as phosphorylation, acetylation, methylation, and ubiquitination. The aberrant sumoylation plays some roles in carcinogenesis. However, the expression pattern of small ubiquitin-related modifier (SUMO)-2/3 in the colorectal cancer has not been reported. We assessed the expression of SUMO-2/3 and evaluated the expression pattern in colorectal cancer. METHODS: The SUMO-2/3 expression was tested in one normal colon mucosal cell line and 5 colorectal cancer cell lines by Western blot. We collected 322 cases of colorectal cancer operated from January 2000 to December 2010 at Soonchunhyang University Cheonan Hospital. We fabricated the tissue microarray and the expression of SUMO-2/3 was evaluated by immunohistochemistry. The results were analyzed with clinicopathologic parameters. RESULTS: The SUMO-2/3 was not expressed in the normal colon mucosal cell line. However, it was expressed highly in all the 5 colorectal cancer cell lines as the beta-actin. The SUMO-2/3 was expressed in 68.3% of the colorectal cancers and its expression was correlated with the pathological tumor stage stage (odds ratio, 2.89; 95% confidence interval, 1.10 to 7.55; P=0.031). CONCLUSION: The SUMO-2/3 plays some roles in carcinogenesis and progression of the colorectal cancer.


Subject(s)
Acetylation , Actins , Blotting, Western , Cell Line , Colon , Colorectal Neoplasms , Genes, Tumor Suppressor , Immunohistochemistry , Incidence , Korea , Life Style , Methylation , Oncogenes , Phosphorylation , Protein Processing, Post-Translational , Proteins , Sumoylation , Tissue Array Analysis , Ubiquitin , Ubiquitination
20.
Chinese Journal of Biotechnology ; (12): 952-962, 2011.
Article in Chinese | WPRIM | ID: wpr-324482

ABSTRACT

Nowadays, SUMO fusion system is important for recombinant protein production in Escherichia coli, yet a few aspects remain to be improved, including the efficacy for vector construction and protein solubility. In this study, we found the SUMO gene Smt3 (Sm) of Saccharomyces cerevisiae conferred an unexpected activity of constitutive prokaryotic promoter during its PCR cloning, and the gene coding regions of SUMOs in most species had a sigma70-dependent prokaryotic promoter embedded, through the prediction via the BPROM program developed by Softberry. By combining the characters of Sm promoter activity and the Stu I site (added at the 3'-terminal of Sm), and introducing a His-tag and a hyper-acidic solubility-enhancing tag, we further constructed a set of versatile vectors for gene cloning and expression on the basis of Sm'-LacZa fusion gene. Experimentally started from these vectors, several target genes were subcloned and expressed through blue-white screening and SDS-PAGE analysis. The results manifest a few of expectable advantages such as rapid vector construction, highly soluble protein expression and feasible co-expression of correlated proteins. Conclusively, our optimized SUMO fusion technology herein could confer a large potential in E. coli protein expression system, and the simultaneously established co-expression vector systems could also be very useful in studying the protein-protein interactions in vivo.


Subject(s)
Amino Acid Sequence , Base Sequence , Escherichia coli , Genetics , Metabolism , Genetic Vectors , Genetics , Lac Operon , Genetics , Molecular Sequence Data , Promoter Regions, Genetic , Genetics , Recombinant Fusion Proteins , Genetics , Saccharomyces cerevisiae Proteins , Genetics , Small Ubiquitin-Related Modifier Proteins , Genetics , Sumoylation
SELECTION OF CITATIONS
SEARCH DETAIL