1.Sumoylation and its role in hematological disease.
Journal of Experimental Hematology 2013;21(1):218-221
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.
Animals
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Hematologic Diseases
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pathology
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therapy
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Humans
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Sumoylation
2.Transcriptional activation of nuclear estrogen receptor and progesterone receptor and its regulation.
Qi-Liang XIN ; Jing-Tao QIU ; Sheng CUI ; Guo-Liang XIA ; Hai-Bin WANG
Acta Physiologica Sinica 2016;68(4):435-454
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.
Ligands
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Phosphorylation
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Receptors, Estrogen
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Receptors, Progesterone
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Sumoylation
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Transcriptional Activation
3.Research Progress in the Function of SUMOylation during Infection by the Influenza Virus.
Huimin LIU ; Wenqing LI ; Lijuan SU ; Guozhi ZHANG ; Yan LI ; Xiao LI ; Hongtao CHANG
Chinese Journal of Virology 2015;31(5):560-564
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.
Animals
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Humans
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Influenza, Human
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virology
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Orthomyxoviridae
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genetics
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metabolism
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Sumoylation
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Viral Proteins
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genetics
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metabolism
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Virus Replication
4.Effects of SUMOylation on the subcellular localization and function of DAXX.
Ling LI ; Juan WEN ; Qin-Hui TUO ; Duan-Fang LIAO
Acta Physiologica Sinica 2013;65(1):89-95
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.
Adaptor Proteins, Signal Transducing
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physiology
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Gene Expression Regulation
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Humans
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Nuclear Proteins
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physiology
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Sumoylation
5.Research Progress of a Novel Pro-apoptosis Gene PNAS-4 in Gene Therapy and Its Molecular Mechanism Hypotheses.
Journal of Biomedical Engineering 2015;32(6):1380-1384
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.
Apoptosis
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Apoptosis Regulatory Proteins
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genetics
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Genetic Therapy
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Humans
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Neoplasms
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therapy
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Sumoylation
6.Post-transcriptional protein modification of Gata4.
Chinese Journal of Contemporary Pediatrics 2012;14(10):800-803
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.
Acetylation
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Animals
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GATA4 Transcription Factor
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chemistry
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genetics
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metabolism
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Humans
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Methylation
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Phosphorylation
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Protein Processing, Post-Translational
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Sumoylation
7.Effect of SUMO Modification on the Chromosomal Aneuploidy in Oocytes.
Yan Ping REN ; Qiong You LIU ; Xiao Can LEI
Acta Academiae Medicinae Sinicae 2019;41(3):419-424
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.
Aneuploidy
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Cell Cycle Proteins
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Chromatids
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Chromosomal Proteins, Non-Histone
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Chromosome Segregation
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Humans
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Microtubules
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Oocytes
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cytology
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Sumoylation
8.Sortilin-induced lipid accumulation and atherogenesis are suppressed by HNF1b SUMOylation promoted by flavone of Polygonatum odoratum.
Fang LIU ; Shirui CHEN ; Xinyue MING ; Huijuan LI ; Zhaoming ZENG ; Yuncheng LV
Journal of Zhejiang University. Science. B 2023;24(11):998-1013
This study aims to investigate the impact of hepatocyte nuclear factor 1β (HNF1b) on macrophage sortilin-mediated lipid metabolism and aortic atherosclerosis and explore the role of the flavone of Polygonatum odoratum (PAOA-flavone)-promoted small ubiquitin-related modifier (SUMO) modification in the atheroprotective efficacy of HNF1b. HNF1b was predicted to be a transcriptional regulator of sortilin expression via bioinformatics, dual-luciferase reporter gene assay, and chromatin immunoprecipitation. HNF1b overexpression decreased sortilin expression and cellular lipid contents in THP-1 macrophages, leading to a depression in atherosclerotic plaque formation in low-density lipoprotein (LDL) receptor-deficient (LDLR-/-) mice. Multiple SUMO1-modified sites were identified on the HNF1b protein and co-immunoprecipitation confirmed its SUMO1 modification. The SUMOylation of HNF1b protein enhanced the HNF1b-inhibited effect on sortilin expression and reduced lipid contents in macrophages. PAOA-flavone treatment promoted SUMO-activating enzyme subunit 1 (SAE1) expression and SAE1-catalyzed SUMOylation of the HNF1b protein, which prevented sortilin-mediated lipid accumulation in macrophages and the formation of atherosclerotic plaques in apolipoprotein E-deficient (ApoE-/-) mice. Interference with SAE1 abrogated the improvement in lipid metabolism in macrophage cells and atheroprotective efficacy in vivo upon PAOA-flavone administration. In summary, HNF1b transcriptionally suppressed sortilin expression and macrophage lipid accumulation to inhibit aortic lipid deposition and the development of atherosclerosis. This anti-atherosclerotic effect was enhanced by PAOA-flavone-facilitated, SAE1-catalyzed SUMOylation of the HNF1b protein.
Mice
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Animals
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Polygonatum/metabolism*
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Sumoylation
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Hepatocyte Nuclear Factor 1-beta/metabolism*
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Atherosclerosis/metabolism*
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Flavones
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Lipids
9.Modulation of the Transcriptional Activity of Peroxisome Proliferator-Activated Receptor Gamma by Protein-Protein Interactions and Post-Translational Modifications.
Tae Hyun KIM ; Mi Young KIM ; Seong Ho JO ; Joo Man PARK ; Yong Ho AHN
Yonsei Medical Journal 2013;54(3):545-559
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.
Gene Expression Regulation
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Homeostasis
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*Models, Genetic
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PPAR gamma/genetics/metabolism/*physiology
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*Protein Processing, Post-Translational
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Sumoylation
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Transcription Factors/metabolism/physiology
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Ubiquitination
10.Sumoylation of Hes6 Regulates Protein Degradation and Hes1-Mediated Transcription.
Jiwon LEE ; Sung Kook CHUN ; Gi Hoon SON ; Kyungjin KIM
Endocrinology and Metabolism 2015;30(3):381-388
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.
Animals
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Blotting, Western
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HeLa Cells
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Humans
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Immunoprecipitation
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Lysine
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Mice
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NIH 3T3 Cells
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Periodicity
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Protein Stability
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Proteolysis*
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Repression, Psychology
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Sumoylation*
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Transcriptional Activation
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Ubiquitin
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Ubiquitination