Curcumin nicotinate increases LDL cholesterol uptake in hepatocytes through IDOL/LDL-R pathway regulation.

BACKGROUND: Curcumin nicotinate (Curtn), derived from curcumin and niacin, reduces serum LDL-C levels, partly due to its influence on PCSK9. This study investigates IDOL's role in Curtn's lipid-lowering effects. OBJECTIVE: To elucidate Curtn's regulation of the IDOL/LDLR pathway and potential molecular mechanisms in hepatocytes. METHODS: Differential metabolites in Curtn-treated HepG2 cells were identified via LC-MS. Molecular docking assessed Curtn's affinity with IDOL. Cholesterol content and LDLR expression effects were studied in high-fat diet Wistar rats. In vitro evaluations determined Curtn's influence on IDOL overexpression's LDL-C uptake and LDLR expression in hepatocytes. RESULTS: Lipids were the main differential metabolites in Curtn-treated HepG2 cells. Docking showed Curtn's higher affinity to IDOL's FERM domain compared to curcumin, suggesting potential competitive inhibition of IDOL's binding to LDLR. Curtn decreased liver cholesterol in Wistar rats and elevated LDLR expression. During in vitro experiments, Curtn significantly enhanced the effects of IDOL overexpression in HepG2 cells, leading to increased LDL-C uptake and elevated expression of LDL receptors. CONCLUSION: Curtn modulates the IDOL/LDLR pathway, enhancing LDL cholesterol uptake in hepatocytes. Combined with its PCSK9 influence, Curtn emerges as a potential hyperlipidemia therapy.

16O/18O- exchange internal standard preparation enhancing reliability of bio-sample natural bioactive compounds absolute quantitation.

Natural bioactive compounds (NBCs) are regarded as candidates for many medical applications widely. Due to the complicated structure and biosynthesis source, only a few NBCs were supplied with commercial isotopic labeled standards. This shortage resulted in poor quantitation reliability in bio-samples for most NBCs, considering the remarkable matrix effects. NBCs metabolism and distribution studies would be restricted consequently. Those properties played critical roles in drug discovery and development. In this study, a fast, convenient, widely adopting 16O/18O exchange reaction was optimized for stable, available, affordable NBCs 18O-labeled standards preparation. With 18O- labeled internal standard, a UPLC-MRM-based NBCs pharmacokinetics analysis strategy was formed. Pharmacokinetics of caffeic acid with Hyssopus Cuspidatus Boriss extract (SXCF) dosed mice was carried out by established strategy. Compared with traditional external standards quantitation, adapting 18O-labeled internal standards, both accuracy and precision were enhanced significantly. Thus, the platform built by this work would accelerate the pharmaceutical research with NBCs, by providing a reliable, wide-adapted, affordable, isotopic internal standard-based bio-samples NBCs absolute quantitation strategy.

The influence of Hyssopus cuspidatus Boriss extract on lipid mediators metabolism network in asthmatic mice.

Current drugs do not provide an absolute cure or modify the course of asthma. Hyssopus cuspidatus Boriss extract (SXCF) has been used as Uyghur medicine for several years to treat bronchial asthma. However, very limited research has been conducted on the therapeutic mechanisms of SXCF. Disruptions in the metabolic network of lipid mediators (LMs) are closely linked to the development of asthma. Here, we explored the therapeutic mechanism of SXCF in asthma based on the metabolic network of LMs, aiming to contribute to the understanding of SXCF in asthma treatment at the molecular level. The UHPLC-MRM strategy was used for the quantitative detection of LMs in the lung tissue and in the peripheral circulatory system (serum). ELISA was used to detect IgE in serum and cytokines in BALF. The lung tissue sections were stained with H&E to observe the infiltration of inflammatory cells, and behavioural changes in mice were observed and recorded throughout the animal experiment. In contrast to the asthma group, the opposite result was observed in the SXCF groups, where the perturbed LMs metabolic network was partly restored in a dose-dependent manner with a significant elevation of anti-inflammatory metabolites, while pro-inflammatory lipids were decreased. As significant downregulation of IgE and pro-inflammatory cytokines was observed, IgE and cytokines analysis also supported the anti-inflammatory effects of SXCF. It was also noticed that SXCF treatment reduced the number of coughs and decreased the inflammatory cell infiltration around the bronchus in mice. These results suggested that SXCF has a significant ameliorative effect on ovalbumin (OVA)-induced asthma. The modulation of LMs is a possible underlying mechanism of the SXCF effects.

Mechanism study of OVA-induced allergic asthma in mice based on lipid metabolomics / 中国药理学通报

Aim To investigate the mechanism and search for potential biomarkers of ovalbumin ( OVA ) -induced asthma in mice base on lipidomics. Methods A BALB/c mouse model of asthma was prepared by OVA. TNF-α, IL-4, IL-10, IFN-γ levels in BALF and IgE level in serum were measured by ELISA. The inflammatory changes in mouse lung tissue were observed using HE staining. Lipid mediators ( LMs) in lung tissue and serum were quantified with UPLC-MS/ MS strategy. Results IgE level in serum and TNF-α, IFN-γ levels in BALF were higher (P <0.05) of asthmatic mice.Typical inflammatory manifestations were seen in lung tissue of asthmatic mice. A total of 57 lipid mediators were quantified with UPLC-MRM. LMs metabolic profiles differed significantly in serum and lung tissue between asthmatic and normal mice, 17 significantly different LMs were found in lung tissue and 6 LMs were found in serum, and the differential metabolites were produced through the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 oxidase (P450) metabolic pathways. Conclusions OVA-induced allergic asthma can cause disorder of lip-id mediators, LMs and cytokines are involved in the occurrence and development of asthma. The differential LMs have potential research value as biomarkers for the development of allergic asthma.

Nicotinate-curcumin inhibits AngII-induced vascular smooth muscle cell phenotype switching by upregulating Daxx expression.

Phenotypic switching is the main cause of the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). We previously showed that Daxx exerted negative regulatory effect on AngII-induced VSMC proliferation and migration. However, the function of Daxx in VSMC phenotype switching remained unknown. Nicotinate-curcumin (NC) is an esterification derivative of niacin and curcumin that can prevent the formation of atherosclerosis. We found that NC significantly decreased AngII-induced VSMC phenotype switching. Furthermore, NC significantly inhibited AngII-induced cell proliferation and migration. Moreover, NC upregulated Daxx expression and regulated the PTEN/Akt signaling pathway. We concluded that NC inhibited AngII-induced VSMC phenotype switching by regulating the PTEN/Akt pathway, and through a mechanism that might be associated with the upregulation of Daxx expression.

Human torpor: translating insights from nature into manned deep space expedition.

During a long-duration manned spaceflight mission, such as flying to Mars and beyond, all crew members will spend a long period in an independent spacecraft with closed-loop bioregenerative life-support systems. Saving resources and reducing medical risks, particularly in mental heath, are key technology gaps hampering human expedition into deep space. In the 1960s, several scientists proposed that an induced state of suppressed metabolism in humans, which mimics 'hibernation', could be an ideal solution to cope with many issues during spaceflight. In recent years, with the introduction of specific methods, it is becoming more feasible to induce an artificial hibernation-like state (synthetic torpor) in non-hibernating species. Natural torpor is a fascinating, yet enigmatic, physiological process in which metabolic rate (MR), body core temperature (Tb ) and behavioural activity are reduced to save energy during harsh seasonal conditions. It employs a complex central neural network to orchestrate a homeostatic state of hypometabolism, hypothermia and hypoactivity in response to environmental challenges. The anatomical and functional connections within the central nervous system (CNS) lie at the heart of controlling synthetic torpor. Although progress has been made, the precise mechanisms underlying the active regulation of the torpor-arousal transition, and their profound influence on neural function and behaviour, which are critical concerns for safe and reversible human torpor, remain poorly understood. In this review, we place particular emphasis on elaborating the central nervous mechanism orchestrating the torpor-arousal transition in both non-flying hibernating mammals and non-hibernating species, and aim to provide translational insights into long-duration manned spaceflight. In addition, identifying difficulties and challenges ahead will underscore important concerns in engineering synthetic torpor in humans. We believe that synthetic torpor may not be the only option for manned long-duration spaceflight, but it is the most achievable solution in the foreseeable future. Translating the available knowledge from natural torpor research will not only benefit manned spaceflight, but also many clinical settings attempting to manipulate energy metabolism and neurobehavioural functions.

Targeting neuroinflammation: The therapeutic potential of ω-3 PUFAs in substance abuse.

Substance abuse is a chronic relapsing disorder that results in serious health and socioeconomic issues worldwide. Addictive drugs induce long-lasting morphologic and functional changes in brain circuits and account for the formation of compulsive drug-seeking and drug-taking behaviors. Yet, there remains a lack of reliable therapy. In recent years, accumulating evidence indicated that neuroinflammation was implicated in the development of drug addiction. Findings from both our and other laboratories suggest that ω-3 polyunsaturated fatty acids (PUFAs) are effective in treating neuroinflammation-related mental diseases, and indicate that they could exert positive effects in treating drug addiction. Thus, in the present review, we summarized and evaluated recently published articles reporting the neuroinflammation mechanism in drug addiction and the immune regulatory ability of ω-3 PUFAs. We also sought to identify some of the challenges ahead in the translation of ω-3 PUFAs into addiction treatment.

Direct Interaction of Daxx and Androgen Receptor Is Required for Their Regulatory Activity in Cholesterol Biosynthesis.

INTRODUCTION: Homeostasis of cholesterol is crucial for cellular function, and dysregulated cholesterol biosynthesis is a metabolic event that can lead to hepatic and cardiovascular abnormalities. OBJECTIVE: The aim of this study was to investigate the effects and mechanisms of domain-associated protein (Daxx) and androgen receptor (AR) on intracellular cholesterol synthesis. METHODS: HepG2 cells were transfected with pCDNA3.1(+)/Daxx plasmid or treated with testosterone propionate to observe the effects of Daxx and AR on intracellular cholesterol levels. Co-immunoprecipitation experiments were performed to identify the interaction between Daxx and AR and to explore the regulatory effects of this interaction on cholesterol synthesis. RESULTS: Our experiments showed that AR promoted cholesterol synthesis and accumulation by activating sterol-regulatory element-binding protein isoform 2. AR-induced cholesterol synthesis was inhibited by Daxx; however, the expression of AR was not affected. Further studies demonstrated the existence of direct binding between Daxx and AR and this interaction was required to suppress AR activity. CONCLUSIONS: The Daxx-mediated antagonism of AR depicts a more complete picture as to how Daxx regulates intracellular cholesterol level and provides a new target for treatment of atherosclerosis.

Pyroptotic cell-derived microparticle: An atherogenic factor in infectious diseases.

Chronic infection is considered a risk factor for atherosclerosis. The link between infectious agents and atherosclerosis is manifested by the presence of infection-induced pyroptotic cells in atherosclerotic lesions. Pyroptosis is an inflammatory form of programmed cell death that occurs most frequently upon infection. However, inflammation is not the only cause by which pyroptosis involved in atherosclerosis. During pyroptosis, a large amount of microparticles are released from pyroptotic cells, which not only transfer inflammatory mediators to arterial vessel, but also mediate the interaction between a variety of cells, leading to endothelial injury, macrophage infiltration, vascular smooth muscle cell migration and proliferation, thereby accelerating atherosclerosis. Thus, we proposed hypothesis that pyroptotic cell-derived microparticle is an atherogenic factor in infectious diseases.

PX Domain-Containing Kinesin KIF16B and Microtubule-Dependent Intracellular Movements.

As a member of the kinesin-3 family, kinesin family member 16B (KIF16B) has a characteristic PhoX homology (PX) domain that binds to membranes containing phosphatidylinositol-3-phosphate (PI(3)P) and moves along microtubule filaments to the plus end via a process regulated by coiled coils in the stalk region in various cell types. The physiological function of KIF16B supports the transport of intracellular cargo and the formation of endosomal tubules. Ras-related protein (Rab) coordinates many steps of membrane transport and are involved in the regulation of KIF16B-mediated vesicle trafficking. Data obtained from clinical research suggest that KIF16B has a potential effect on the disease processes in intellectual disability, abnormal lipid metabolism, and tumor brain metastasis. In this review, we summarize recent advances in the structural and physiological characteristics of KIF16B as well as diseases associated with KIF16B disorders, and speculating its role as a potential adaptor for intracellular cholesterol trafficking.

Curcumin: From a controversial "panacea" to effective antineoplastic products.

BACKGROUND: Curcumin, a controversial "panacea," has been broadly studied. Its bioactivities including antioxidant, anti-inflammatory, and especially antineoplastic activities have been documented. However, due to its extensive bioactivities, some scientists hold a skeptical point of view toward curcumin and described curcumin as a "deceiver" to chemists. The objective of this study was to explore curcumin's another possibility as a potential supplementary leading compound to cancer treatments. METHODS: Literature searches were conducted using electronic databases. Search terms such as "curcumin," "curcumin analogues," and so on were used. The literatures were collected and summarized. In this article, reported targets of curcumin are reviewed. The limitations of a curcumin as a therapeutic anticancer product including low bioavailability and poor targeting are mentioned. Furthermore, modified curcumin analogues and antitumor mechanisms are listed and discussed in the aspects of cell death and tumor microenvironment including angiogenesis, tissue hypoxia status, and energy metabolism. RESULTS: Several possible modification strategies were presented by analyzing the relationships between the antitumor activity of curcumin analogues and their structural characteristics, including the introduction of hydrophilic group, shortening of redundant hydrocarbon chain, the introduction of extra chemical group, and so on. CONCLUSIONS: From our perspective, after structural modification curcumin could be more effective complementary product for cancer therapies by the enhancement of targeting abilities and the improvement of bioavailability.

Cholesterol in LDL receptor recycling and degradation.

The SREBP2/LDLR pathway is sensitive to cholesterol content in the endoplasmic reticulum (ER), while membrane low-density lipoprotein receptor (LDLR) is influenced by sterol response element binding protein 2 (SREBP2), pro-protein convertase subtilisin/kexin type 9 (PCSK9) and inducible degrader of LDLR (IDOL). LDL-C, one of the risk factors in cardiovascular disease, is cleared through endocytosis recycling of LDLR. Therefore, we propose that a balance between LDLR endocytosis recycling and PCSK9-mediated and IDOL-mediated lysosomal LDLR degradation is responsible for cholesterol homeostasis in the ER. For statins that decrease serum LDL-C levels via cholesterol synthesis inhibition, the mechanism by which the statins increase the membrane LDLR may be regulated by cholesterol homeostasis in the ER.

Resolving neuroinflammation, the therapeutic potential of the anti-malaria drug family of artemisinin.

Artemisinin (Qinghaosu) and its semi-synthetic derivatives have been demonstrated to alleviate neuroinflammatory response in the central nerve system (CNS). In this review, we summarized that artemisinins are capable to treat neuroinflammtion-related CNS diseases in both direct (via regulating inflammatory process in the CNS, exerting anti-oxidative stress and neuroprotective effect, and preventing Aß accumulation) and indirect (via maintaining BBB integrity, suppressing systemic inflammation and alleviating intestinal inflammtion) manner. However, the precise mechanism of their anti-neuroinflammatory effects and potential neurotoxicity, which hindered further progress in these aspects, remains unclear. We suggest that further understanding of the PK/PD properties and structure-action relationship of atemisinin and its derivatives will facilitate the development of new therapeutics with better curative effects and safety.

Curcumin enhances vascular contractility via induction of myocardin in mouse smooth muscle cells.

A variety of cardiovascular diseases is accompanied by the loss of vascular contractility. This study sought to investigate the effects of curcumin, a natural polyphenolic compound present in turmeric, on mouse vascular contractility and the underlying mechanisms. After mice were administered curcumin (100 mg·kg-1·d-1, ig) for 6 weeks, the contractile responses of the thoracic aorta to KCl and phenylephrine were significantly enhanced compared with the control group. Furthermore, the contractility of vascular smooth muscle (SM) was significantly enhanced after incubation in curcumin (25 µmol/L) for 4 days, which was accompanied by upregulated expression of SM marker contractile proteins SM22α and SM α-actin. In cultured vascular smooth muscle cells (VSMCs), curcumin (10, 25, 50 µmol/L) significantly increased the expression of myocardin, a "master regulator" of SM gene expression. Curcumin treatment also significantly increased the levels of caveolin-1 in VSMCs. We found that as a result of the upregulation of caveolin-1, curcumin blocked the activation of notch1 and thereby abolished Notch1-inhibited myocardin expression. Knockdown of caveolin-1 or activation of Notch1 signaling with Jagged1 (2 µg/mL) diminished these effects of curcumin in VSMCs. These findings suggest that curcumin induces the expression of myocardin in mouse smooth muscle cells via a variety of mechanisms, including caveolin-1-mediated inhibition of notch1 activation and Notch1-mediated repression of myocardin expression. This may represent a novel pathway, through which curcumin protects blood vessels via the beneficial regulation of SM contractility.

Ablation of endothelial prolyl hydroxylase domain protein-2 promotes renal vascular remodelling and fibrosis in mice.

Accumulating evidence demonstrates that hypoxia-inducible factor (HIF-α) hydroxylase system has a critical role in vascular remodelling. Using an endothelial-specific prolyl hydroxylase domain protein-2 (PHD2) knockout (PHD2EC KO) mouse model, this study investigates the regulatory role of endothelial HIF-α hydroxylase system in the development of renal fibrosis. Knockout of PHD2 in EC up-regulated the expression of HIF-1α and HIF-2α, resulting in a significant decline of renal function as evidenced by elevated levels of serum creatinine. Deletion of PHD2 increased the expression of Notch3 and transforming growth factor (TGF-ß1) in EC, thus further causing glomerular arteriolar remodelling with an increased pericyte and pericyte coverage. This was accompanied by a significant elevation of renal resistive index (RI). Moreover, knockout of PHD2 in EC up-regulated the expression of fibroblast-specific protein-1 (FSP-1) and increased interstitial fibrosis in the kidney. These alterations were strongly associated with up-regulation of Notch3 and TGF-ß1. We concluded that the expression of PHD2 in endothelial cells plays a critical role in renal fibrosis and vascular remodelling in adult mice. Furthermore, these changes were strongly associated with up-regulation of Notch3/TGF-ß1 signalling and excessive pericyte coverage.

LPS causes pericyte loss and microvascular dysfunction via disruption of Sirt3/angiopoietins/Tie-2 and HIF-2α/Notch3 pathways.

Recent studies reveal a crucial role of pericyte loss in sepsis-associated microvascular dysfunction. Sirtuin 3 (SIRT3) mediates histone protein post-translational modification related to aging and ischemic disease. This study investigated the involvement of SIRT3 in LPS-induced pericyte loss and microvascular dysfunction. Mice were exposed to LPS, expression of Sirt3, HIF-2α, Notch3 and angiopoietins/Tie-2, pericyte/endothelial (EC) coverage and vascular permeability were assessed. Mice treated with LPS significantly reduced the expression of SIRT3, HIF-2α and Notch3 in the lung. Furthermore, exposure to LPS increased Ang-2 while inhibited Ang-1/Tie-2 expression with a reduced pericyte/EC coverage. Intriguingly, knockout of Sirt3 upregulated Ang-2, but downregulated Tie-2 and HIF-2α/Notch3 expression which resulted in a dramatic reduction of pericyte/EC coverage and exacerbation of LPS-induced vascular leakage. Conversely, overexpression of Sirt3 reduced Ang-2 expression and increased Ang-1/Tie-2 and HIF-2α/Notch3 expression in the LPS treated mice. Overexpression of Sirt3 further prevented LPS-induced pericyte loss and vascular leakage. This was accompanied by a significant reduction of the mortality rate. Specific knockout of prolyl hydroxylase-2 (PHD2) increased HIF-2α/Notch3 expression, improved pericyte/EC coverage and reduced the mortality rate in the LPS-treated mice. Our study demonstrates the importance of SIRT3 in preserving vascular integrity by targeting pericytes in the setting of LPS-induced sepsis.

IDOL, inducible degrader of low-density lipoprotein receptor, serves as a potential therapeutic target for dyslipidemia.

Low-density lipoprotein cholesterol (LDL-C) is the hall marker for the atherosclerotic cardiovascular disease (ASCVD). It has been shown that over 70% of circulating LDL-C is metabolized through binding and activation of hepatic LDL receptor (LDLR). Genetic LDLR mutations cause hypercholesterolemia in the patients. Therefore, elevation of LDLR levels is beneficial for the treatment of dyslipidemia. LDLR expression is regulated by the SREBP2/PCSK9 pathways. Targeting SREBP2/PCSK9 pathways by statins and human monoclonal PCSK9 antibody has been shown to reduce the progression of ASVCD. Recent studies identified that inducible degrader of LDLR (IDOL) is a novel regulator of LDLR. IDOL is an E3-ubiquitin ligase regulated via liver X receptors (LXRs) binding to the upstream of translation start site of IDOL. IDOL modulates LDLR distribution through ubiquitination and degradation of LDLR in lysosomes. Genome-wide association studies (GWAS) have revealed that the nonsynonymous substitution rs9370867 of IDOL probably contributes to the variability of circulating LDL levels. Recently studies also demonstrated that IDOL influences PCSK9 expression in a LDLR/SREBP2-dependent manner. Based upon these novel findings, we hypothesize that IDOL and PCSK9 would have a synergistic effect on LDLR distribution. Specifically, loss of IDOL increases LDLR distribution in the hepatic cell, and subsequently reduces serum LDL-C levels in dyslipidemic patients. IDOL might be a potential therapeutic target for the treatment of ASCVD.

Apelin Gene Therapy Increases Autophagy via Activation of Sirtuin 3 in Diabetic Heart.

Heart failure is the leading cause of death in diabetic patients. Recently we showed that apelin gene therapy attenuates heart failure following myocardial infarction. This study further explored the potential mechanisms by which apelin may reduce cardiac injury in Postmyocardial infarction (MI)) model of diabetes. Wild type and Sirt3 knockout (Sirt3 KO) mice were induced into diabetes by intra-peritoneal (i.p.) Streptozotocin (STZ). STZ mice were then subjected to MI followed by immediate intramyocardial injection with Adenovirus-apelin (Ad-apelin). Ad-apelin treatment resulted in over expression of apelin in the ischemic hearts of STZ mice. Apelin over expression led to a significant increase in Sirt3 expression. Apelin over expression significantly reduced gp91phox expression. This was accompanied by a significant reduction of reactive oxygen species formation. Ad-apelin treatment also dramatically reduced NF-κb-p65 expression in WT-STZ mice. Over expression of apelin further enhanced autophagy markers (LC3-II and beclin-1) expression in post-MI heart. Most intriguingly, knockout of Sirt3 in STZ mice abolished these beneficial effects of apelin treatment. In vitro, knockout of Sirt3 in EPCs significantly enhanced high glucose-induced ROS formation. Conversely, treatment of Sirt3 KO-EPCs with NADPH oxidase inhibitor led to two fold increase in LC3-II levels. Our studies demonstrate that apelin increases autophagy via up regulation of Sirt3 and suppression of ROS-NF-κb pathway in diabetic heart.

Ezetimibe-mediated protection of vascular smooth muscle cells from cholesterol accumulation through the regulation of lipid metabolism-related gene expression.

BACKGROUND: Ezetimibe is a potent inhibitor of Niemann-Pick type C1-Like 1 and has been approved for the treatment of hypercholesterolemia. Our preliminary study showed that ezetimibe promotes cholesterol efflux from vascular smooth muscle cells (VSMCs). Our aim was to investigate the cellular mechanisms underlying the ezetimibe actions. METHODS AND RESULTS: Rat VSMCs were converted to foam cells by incubation with cholesterol:methyl-ß-cyclodextrin. The intracellular free cholesterol, total cholesterol, and the ratio of cholesteryl ester to total cholesterol were decreased after the incubation of VSMCs with different concentrations of ezetimibe (3, 10, 30, and 30 µmol/l) or treated with 30 µmol/l of ezetimibe for different time periods (6, 12, 24, and 48 h). Our results also showed that the expression of caveolin-1, liver X receptor α, and ATP-binding cassette transporter ABCA1 was enhanced, but the expression of nSREBP-1c was decreased in a concentration- and time-dependent manner. RNA interference was used to determine the roles of caveolin-1 and SREBP-1 in the lipid-lowering effect of ezetimibe. The results showed that caveolin-1 was involved in the regulation of intracellular cholesterol content, and the expression of caveolin-1 was repressed by SREBP-1. CONCLUSION: The present study indicates that ezetimibe protects VSMCs from cholesterol accumulation by regulating the expression of lipid metabolism-related genes.

[Effects of SUMOylation on the subcellular localization and function of DAXX].

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.