• TRIM proteins
• TRIM55
• small ubiquitin-like modifier (SUMO)
• ubiquitin
• ubiquitin ligase

• Humans
• Ubiquitin/metabolism
• SUMO-1 Protein/genetics
• SUMO-1 Protein/metabolism
• Protein Processing, Post-Translational
• Ubiquitin-Protein Ligases/genetics
• Ubiquitin-Protein Ligases/metabolism

• CRLs
• E3 ubiquitin ligase
• cardiomyocyte maturation
• heart development
• proteasomal degradation
• ubiquitin

• Ubiquitin/metabolism
• Cullin Proteins/metabolism
• Ubiquitination
• Ubiquitin-Protein Ligases/metabolism

• R01HL165205 NIH HHS
• R01 HL124248 NHLBI NIH HHS
• R01 HL165205 NHLBI NIH HHS
• R01HL124248 NIH HHS
• R01HL146807A1 NIH HHS
• R01 HL146807 NHLBI NIH HHS

• E3 ubiquitin ligase
• asthma
• cardiac inflammation
• inflammation
• metabolic disorders
• ubiquitination

• Humans
• Insulin Resistance
• Diabetes Mellitus, Type 2
• Ubiquitination
• Ubiquitin-Protein Ligases/genetics
• Ubiquitin-Protein Ligases/metabolism
• Ubiquitin/metabolism
• Tripartite Motif Proteins/genetics
• Tripartite Motif Proteins/metabolism
• Insulins

• 20224BAB216010 Natural Science Foundation of Jiangxi Province
• 202210482 Science and Technology Planning Project of Health Commission of Jiangxi Province
• YFYPY202022 Youth Talent Cultivation Project of the First Affiliated Hospital of Nanchang University

• Ferroptosis
• Mitophagy
• Myocardial ischemia-reperfusion injury
• PINK1/Parkin signaling pathway
• SIRT1-SIRT3 axis

• Humans
• Myocardial Reperfusion Injury/genetics
• Sirtuin 3/genetics
• Sirtuin 3/metabolism
• Sirtuin 1/genetics
• Sirtuin 1/metabolism
• Ferroptosis/genetics
• Signal Transduction
• Protein Kinases/metabolism
• Ubiquitin-Protein Ligases/genetics
• Ubiquitin-Protein Ligases/metabolism

• 20203CCH45008 Introduced and Jointly Built High-end R&D Institute of Jiangxi
• 82060064 the National Natural Science Foundation of China

• TRIM55
• TRIP6
• hepatocellular carcinoma
• proliferation

• cell biology
• stem-cell differentiation
• cell signalling
• phosphorylation
• cardiovascular biology

• DP190101972 Department of Education and Training | Australian Research Council (ARC)
• GNT1160257 Department of Health | National Health and Medical Research Council (NHMRC)
• NNF21CC0073729 Novo Nordisk Fonden (Novo Nordisk Foundation)
• GNTs 2008376, 1160256 and 1160257 Department of Health | National Health and Medical Research Council (NHMRC)
• MR/T005181/1 Medical Research Council
• The Medical Research Future Fund, MRF2007316, MRF2007471 Heart Foundation of Australia, 104997, 105146

• Deubiquitylation
• Glioma
• TRIM56
• cIAP1

• M-band
• cardiomyopathy
• hiPSC-CM
• phosphoproteomics
• pseudokinase, α-kinase
• sarcomere

Gastric cancer (GC) is considered a major global health problem. The role of TRIM55, a member of the three-domain protein family, in GC is unknown.

To determine the expression of TRIM55 in GC tissues and its relationship with clinicopathological characteristics, and to investigate the effects of TRIM55 on the malignant biological behavior of GC cells.

Differential expression of TRIM55 in GC and para-cancer tissues was detected by immunohistochemistry, and the relationship between TRIM55 level and clinicopathological characteristics and prognosis was analyzed. Gain-of-function, loss-of-function, cell counting kit-8 assay, colony formation, transwell assay, wound healing assay, and western blot analysis were used to assess the potential role of TRIM55 in the development of GC.

TRIM55 expression was significantly increased in GC tissues compared with adjacent normal tissues. High expression of TRIM55 was associated with advanced pathological stage and poor prognosis. Overexpression of TRIM55 promoted invasion and metastasis of GC cells in vitro by regulating epithelial-mesenchymal transition (EMT), whereas knockdown of TRIM55 had the opposite effect. Our data showed that TRIM55 is highly expressed in GC tissues, and is associated with poor prognosis. TRIM55 plays the role of an oncogene in GC, and it promotes metastasis of GC through the regulation of EMT.

TRIM55 may be a possible target for the diagnosis and prognosis of GC patients.

• TRIM55
• Gastric cancer
• Prognosis
• Epithelial-mesenchymal transition

Sarcomeres are mainly composed of filament and signaling proteins and are the smallest molecular units of muscle contraction and relaxation. The sarcomere protein titin serves as a molecular spring whose stiffness mediates myofilament extensibility in skeletal and cardiac muscle. Due to the enormous size of titin and its tight integration into the sarcomere, the incorporation and degradation of the titin filament is a highly complex task. The details of the molecular processes involved in titin turnover are not fully understood, but the involvement of different intracellular degradation mechanisms has recently been described. This review summarizes the current state of research with particular emphasis on the relationship between titin and protein quality control. We highlight the involvement of the proteasome, autophagy, heat shock proteins, and proteases in the protection and degradation of titin in heart and skeletal muscle. Because the fine-tuned balance of degradation and protein expression can be disrupted under pathological conditions, the review also provides an overview of previously known perturbations in protein quality control and discusses how these affect sarcomeric proteins, and titin in particular, in various disease states.

• Deutsche Forschungsgemeinschaft
• Else Kröner-Fresenius-Stiftung

• HFpEF
• aging
• amyloidosis
• electromechanical uncoupling
• heart failure
• transthyretin

• Amyloid Neuropathies, Familial
• Animals
• Calcium
• Calcium, Dietary
• Heart Failure
• Mice
• Myocytes, Cardiac
• Prealbumin/chemistry
• Prealbumin/pharmacology
• Rats
• Sarcomeres
• Stroke Volume

• R01 HL132871 NHLBI NIH HHS
• Foundation for the National Institutes of Health

Up until now, cancer refractoriness and distal organ metastatic disease remain as major obstacles for oncologists to achieve satisfactory therapeutic effects for lung adenocarcinoma patients. Previous studies indicated that TRIM55, which participates in the natural development of muscle and cardiovascular system, plays a protective role in hepatocellular carcinoma (HCC) pathogenesis. Therefore, in this study, we aimed to unveil the detailed molecular mechanism of TRIM55 and identify the potential target for lung adenocarcinoma patients. Surgical samples and lung cancer cell lines were collected to detect the TRIM55 expression for patients with or without lymph node/distal organ metastasis. Cellular functional assays including transwell assay, wound healing assay, cellular survivability assay, etc. as well as ubiquitination assay were performed to evaluate the impact of TRIM55/Snail1 regulatory network via the UPP pathway on lung cancer tumor cell migration and chemo-resistance. Lung cancer tissues and tumor cell lines exhibited significantly lower levels of TRIM55 expression. Functional study further indicated that TRIM55 inhibited chemo-resistance, migration, and cancer stem-cell like phenotype of tumor cells. Further detailed molecular experiments indicated that TRIM55 promoted degradation of Snail1 via the UPP pathway, which played an interesting role in the regulation of cancer cell malignancy. This study provided novel theory that TRIM55 acted as a potential tumor suppressor by inhibition of tumor cell malignancy through enhancement of Snail1 degradation via the UPP pathway. Our research will inspire further exploration on TRIM55 to promote therapeutic effects for lung adenocarcinoma patients.

• Lung adenocarcinoma
• snail1
• trim55
• tumor suppressor
• upp pathway

Accumulating evidence demonstrates that dysregulation of ubiquitin-mediated degradation of oncogene or suppressors plays an important role in several diseases. However, the function and molecular mechanisms of ubiquitin ligases underlying hepatocellular carcinoma (HCC) remain elusive. In the current study, we show that overexpression of TRIM54 was associated with HCC progression. TRIM54 overexpression facilitates proliferation and lung metastasis; however, inhibition of TRIM54 significantly suppressed HCC progression both in vitro and in vivo. Mechanically, we demonstrated that TRIM54 directly interacts with Axis inhibition proteins 1 (Axin1) and induces E3 ligase-dependent proteasomal turnover of Axin1 and substantially induces sustained activation of wnt/β-catenin in HCC cell lines. Furthermore, we showed that inhibition of the wnt/β-catenin signaling pathway via small molecule inhibitors significantly suppressed TRIM54-induced proliferation. Our data suggest that TRIM54 might function as an oncogenic gene and targeting the TRIM54/Axin1/β-catenin axis signaling may be a promising prognostic factor and a valuable therapeutic target for HCC.

• TRIM54
• Wnt/β-catenin signaling
• hepatocellular carcinoma
• metastasis
• proliferation
• ubiquitination

The sarcomere protein titin is a major determinant of cardiomyocyte stiffness and ventricular distensibility. The constant mechanical stress on titin requires well-controlled protein quality control, the exact mechanisms of which have not yet been fully elucidated. Here, we analyzed E3-ligases potentially responsible for cardiac titin ubiquitination and specifically studied the involvement of the autophagosomal system in titin degradation. Pharmacological inhibition of autophagy and the proteasome in cultured primary rat cardiomyocytes significantly elevated titin ubiquitination and increased titin degradation. Using in-vitro pull down assays we identified binding of E3-ligases MuRF1-3, CHIP and Fbx32 to several titin domains. Immunofluorescence analysis showed sarcomeric localization of the E3-ligases. siRNA-mediated knock-down of the E3-ligases MuRF-1, -3 and a combination of CHIP/Fbx32 significantly reduced autophagy-related titin ubiquitination, whereas knock-down of MuRF-2 and -3 reduced proteasome-related titin ubiquitination. We demonstrated that the proteasomal and the autophagosomal-lysosomal system participate in degradation of the titin filament. We found that ubiquitination and degradation of titin are partially regulated by E3-ligases of the MuRF family. We further identified CHIP and Fbx32 as E3-ligases involved in titin ubiquitination.

• Cardiac disease
• Cardiac sarcomere mechanics
• Titin

• american heart association
• european research council
• deutsche forschungsgemeinschaft

• Mechanotransduction
• Myofibrillogenesis
• Phosphatidylinositol 4,5-bisphosphate
• Proteomics
• Signaling pathway

• Cardiac disease
• Proteostasis
• Tripartite motif-containing proteins (TRIMs)

• CRISPR/Cas9
• Genetic variation
• Heart failure
• TRIM55
• rs138811034

• atrophy
• autophagy
• methyltransferases
• p97
• skeletal muscle

Cyclooxygenases (COXs), including COX-1 and -2, are enzymes essential for lipid mediator (LMs) syntheses from arachidonic acid (AA), such as prostaglandins (PGs). Furthermore, COXs could interplay with other enzymes such as lipoxygenases (LOXs) and cytochrome P450s (CYPs) to regulate the signaling of LMs. In this study, to comprehensively analyze the function of COX-1 and -2 in regulating the signaling of bioactive LMs in skeletal muscle, mouse primary myoblasts and C2C12 cells were transfected with specific COX-1 and -2 siRNAs, followed by targeted lipidomic analysis and customized quantitative PCR gene array analysis. Knocking down COXs, particularly COX-1, significantly reduced the release of PGs from muscle cells, especially PGE₂ and PGF_2α, as well as oleoylethanolamide (OEA) and arachidonoylethanolamine (AEA). Moreover, COXs could interplay with LOXs to regulate the signaling of hydroxyeicosatetraenoic acids (HETEs). The changes in LMs are associated with the expression of genes, such as Itrp1 (calcium signaling) and Myh7 (myogenic differentiation), in skeletal muscle. In conclusion, both COX-1 and -2 contribute to LMs production during myogenesis in vitro, and COXs could interact with LOXs during this process. These interactions and the fine-tuning of the levels of these LMs are most likely important for skeletal muscle myogenesis, and potentially, muscle repair and regeneration.

• Cyclooxygenase
• lipidomics
• myogenic differentiation
• skeletal muscle

Fibroblasts are a highly heterogeneous population of cells, being found in a large number of different tissues. These cells produce the extracellular matrix, which is essential to preserve structural integrity of connective tissues. Fibroblasts are frequently engaged in migration and remodeling, exerting traction forces in the extracellular matrix, which is crucial for matrix deposition and wound healing. In addition, previous studies performed on primary myoblasts suggest that the E3 ligase MuRF2 might function as a cytoskeleton adaptor. Here, we hypothesized that MuRF2 also plays a functional role in skeletal muscle fibroblasts. We found that skeletal muscle fibroblasts express MuRF2 and its siRNA knock-down promoted decreased fibroblast migration, cell border accumulation of polymerized actin, and down-regulation of the phospho-Akt expression. Our results indicated that MuRF2 was necessary to maintain the actin cytoskeleton functionality in skeletal muscle fibroblasts via Akt activity and exerted an important role in extracellular matrix remodeling in the skeletal muscle tissue.

Macroautophagy/autophagy is a multistep cellular process that sequesters cytoplasmic components for lysosomal degradation. BECN1/Beclin1 is a central protein that assembles cofactors for the formation of a BECN1-PIK3C3-PIK3R4 complex to trigger the autophagy protein cascade. Discovering the regulators of BECN1 is important for understanding the mechanism of autophagy induction. Here, we demonstrate that TRIM59, a tripartite motif protein, plays an important role in autophagy regulation in non-small cell lung cancer (NSCLC). On the one hand, TRIM59 regulates the transcription of BECN1 through negatively modulating the NFKB pathway. On the other hand, TRIM59 regulates TRAF6 induced K63-linked ubiquitination of BECN1, thus affecting the formation of the BECN1-PIK3C3 complex. We further demonstrate that TRIM59 can mediate K48-linked ubiquitination of TRAF6 and promote the proteasomal degradation of TRAF6. Taken together, our findings reveal novel dual roles for TRIM59 in autophagy regulation by affecting both the transcription and the ubiquitination of BECN1.

Abbreviations: ACTB: actin beta; BECN1: beclin 1; CHX: cycloheximide; CQ: chloroquine; GFP: green fluorescent protein; HA: haemagglutinin tag; His: polyhistidine tag; LC3B: microtubule associated protein 1 light chain 3 beta; NFKB: nuclear factor kappa B; NFKBIA: NFKB inhibitor alpha; NSCLC: non-small cell lung cancer; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; RELA: RELA proto-oncogene, NF-kB subunit; SQSTM1: sequestosome 1; tGFP: Turbo green fluorescent protein; TRAF6: TNF receptor associated factor 6; TRIM59: tripartite motif containing 59; B: ubiquitin

• Autophagy
• BECN1
• NSCLC
• TRAF6
• TRIM59
• ubiquitination

Pregnancy and parturition are intricately regulated to ensure successful reproductive outcomes. However, the factors that control gestational length in humans and other anthropoid primates remain poorly defined. Here, we show the endogenous retroviral long terminal repeat transposon-like human element 1B (THE1B) selectively controls placental expression of corticotropin-releasing hormone (CRH) that, in turn, influences gestational length and birth timing. Placental expression of CRH and subsequently prolonged gestational length were found in two independent strains of transgenic mice carrying a 180-kb human bacterial artificial chromosome (BAC) DNA that contained the full length of CRH and extended flanking regions, including THE1B. Restricted deletion of THE1B silenced placental CRH expression and normalized birth timing in these transgenic lines. Furthermore, we revealed an interaction at the 5′ insertion site of THE1B with distal-less homeobox 3 (DLX3), a transcription factor expressed in placenta. Together, these findings suggest that retroviral insertion of THE1B into the anthropoid primate genome may have initiated expression of CRH in placental syncytiotrophoblasts via DLX3 and that this placental CRH is sufficient to alter the timing of birth.

The proper timing of delivery is critical during pregnancy; if too early or too late, the baby will be at risk of serious health problems and even death. Corticotropin-releasing hormone (CRH) is a protein that can be detected in maternal blood, and its concentration correlates with the timing of birth. In humans and other anthropoid primates, CRH is made by the placenta, whereas in other mammals, it is produced in a specialized region of the brain. To understand the regulation and evolution of this key protein, we inserted the human CRH gene and nearby regions into the mouse genome, which resulted in human CRH expression in the mouse placenta. Mouse litters that make CRH in their placentas are born later than control mice, showing that CRH can directly affect birth timing. Using our mouse model, we then selectively deleted a remnant of an ancient retrovirus that is normally found in the DNA of anthropoid primates and demonstrated that this specific region controls expression of CRH in the placenta. Deletion of this region also restored normal birth timing in the mice by eliminating CRH production from the placenta. We propose that retroviral regulation of CRH in the placenta may be a mechanism of controlling birth timing in humans and other anthropoid primates.

• Animals
• Base Sequence
• CRISPR-Cas Systems/genetics
• Chromosomes, Artificial, Bacterial/genetics
• Corticotropin-Releasing Hormone/genetics
• Corticotropin-Releasing Hormone/metabolism
• Female
• Gene Regulatory Networks
• Homeodomain Proteins/metabolism
• Humans
• Male
• Mice, Transgenic
• Mutagenesis, Insertional/genetics
• Parturition
• Placenta/metabolism
• Pregnancy
• Primates/genetics
• Protein Binding
• Retroelements/genetics
• Sequence Deletion
• Species Specificity
• Terminal Repeat Sequences/genetics
• Transcription Factors/metabolism
• Trophoblasts/metabolism

• R01 HD091527 NICHD NIH HHS
• R21 HD090196 NICHD NIH HHS
• T32 GM063483 NIGMS NIH HHS

• E3 ligase
• TRIM
• Ubiquitination

• Animals
• Heart Diseases/enzymology
• Heart Diseases/pathology
• Heart Diseases/physiopathology
• Humans
• Myocardium/enzymology
• Myocardium/pathology
• Proteostasis
• Substrate Specificity
• Tripartite Motif Proteins/metabolism
• Ubiquitin-Protein Ligases/metabolism
• Ubiquitination

• Autophagy
• TRIM
• Ubiquitination

• Animals
• Humans
• Muscle Contraction/physiology
• Muscle Proteins/genetics
• Muscle Proteins/physiology
• Muscle, Skeletal/metabolism
• Muscle, Skeletal/physiology
• Muscular Diseases/metabolism
• Mutation
• Myofibrils/metabolism
• Myofibrils/physiology
• Myosins/genetics
• Myosins/physiology
• Sarcomeres/physiology

• T32 AR007592 NIAMS NIH HHS

• hepatitis
• lipopolysaccharide
• macrophage
• muscle RING‐finger 2
• nuclear factor‐κB

MyBPC: A muscle protein for all seasons.

Myosin-binding protein C (MyBPC) in the muscle sarcomere interacts with several contractile and structural proteins. Mutations in the cardiac isoform (MyBPC-3) in humans, or animal knockout, are associated with cardiomyopathy. Function of the fast skeletal isoform (MyBPC-2) in living muscles is less understood. This question was addressed using zebrafish models, combining gene expression data with functional analysis of contractility and small-angle x-ray diffraction measurements of filament structure. Fast skeletal MyBPC-2B, the major isoform, was knocked down by >50% using morpholino antisense nucleotides. These morphants exhibited a skeletal myopathy with elevated apoptosis and up-regulation of factors associated with muscle protein degradation. Morphant muscles had shorter sarcomeres with a broader length distribution, shorter actin filaments, and a wider interfilament spacing compared with controls, suggesting that fast skeletal MyBPC has a role in sarcomere assembly. Active force was reduced more than expected from the decrease in muscle size, suggesting that MyBPC-2 is required for optimal force generation at the cross-bridge level. The maximal shortening velocity was significantly increased in the MyBPC-2 morphants, but when related to the sarcomere length, the difference was smaller, reflecting that the decrease in MyBPC-2B content and the resulting myopathy were accompanied by only a minor influence on filament shortening kinetics. In the controls, equatorial patterns from small-angle x-ray scattering revealed that comparatively few cross-bridges are attached (as evaluated by the intensity ratio of the 11 and 10 equatorial reflections) during active contraction. X-ray scattering data from relaxed and contracting morphants were not significantly different from those in controls. However, the increase in the 11:10 intensity ratio in rigor was lower compared with that in controls, possibly reflecting effects of MyBPC on the cross-bridge interactions. In conclusion, lack of MyBPC-2 results in a severe skeletal myopathy with structural changes and muscle weakness.

Reduction of Lepeophtheirus salmonis infection in Atlantic salmon achieved by glucosinolates (GLs) from Brassica plants was recently reported. However, wider application of functional feeds based on GLs requires better knowledge of their positive and adverse effects.

Liver, distal kidney and muscle transcriptomes of salmon exposed to the extreme dose of GLs were profiled by microarray, while qPCR analysis followed up selected hepatic and renal responses under the extreme and moderate GLs dose during the L. salmonis challenge. Transcriptional analysis were complemented with measurements of organ indices, liver steatosis and plasma profiling, including indicators of cytolysis and bilirubin. Finally, the third trial was performed to quantify the effect of lower GLs doses on growth.

The extreme GLs dose caused a decrease in hepatic fat deposition and growth, in line with microarray findings, which suggested tissue remodeling and reduction of cellular proliferation in the skeletal muscle and liver. Lower GLs inclusion levels in a follow-up trial did not show negative effects on growth. Microarray analysis of the distal kidney pointed to activation of anti-fibrotic responses under the overexposure. However, analyses of ALT, CK and AST enzymes in plasma provided no evidence of increased cytolysis and organ damage. Prevalent activation of phase-2 detoxification genes that occurred in all three tissues could be considered part of beneficial effects caused by the extreme dose of GLs. In addition, transcriptomic evidence suggested GLs-mediated iron and heme withdrawal response, including increased heme degradation in muscle (upregulation of heme oxygenase-1), decrease of its synthesis in liver (downregulation of porphobilinogen deaminase) and increased iron sequestration from blood (hepatic induction of hepcidin-1 and renal induction of intracellular storage protein ferritin). This response could be advantageous for salmon upon encountering lice, which depend on the host for the provision of iron carrying heme. Most of the hepatic genes studied by qPCR showed similar expression levels in fish exposed to GLs, lice and their combination, while renal induction of leptin suggested heightened stress by the combination of extreme dose of GLs and lice. High expression of interferonγ (cytokine considered organ-protective in mammalian kidney) was detected at the moderate GLs level. This fish also showed highest plasma bilirubin levels (degradation product of heme), and had lowest number of attached lice, further supporting hypothesis that making heme unavailable to lice could be part of an effective anti-parasitic strategy.

Modulation of detoxification and iron metabolism in Atlantic salmon tissues could be beneficial prior and during lice infestations. Investigation of anti-lice functional feeds based on low and moderate GLs inclusion levels thus deserves further attention.

The online version of this article (doi:10.1186/s13071-016-1921-7) contains supplementary material, which is available to authorized users.

• Antioxidant
• Atlantic salmon
• Detoxification
• Functional feeds
• Glucosinolates
• Iron
• Lepeophtheirus salmonis
• Salmo salar
• Salmon louse

• Autophagy
• Heart failure
• Metabolism
• Therapy
• Ubiquitin ligases
• Ubiquitin-proteasome system

• Animals
• Autophagy
• Heart Diseases/metabolism
• Heart Diseases/pathology
• Heart Diseases/therapy
• Humans
• Lysosomes/metabolism
• Lysosomes/pathology
• Myocardium/metabolism
• Myocardium/pathology
• Myocytes, Cardiac/metabolism
• Myocytes, Cardiac/pathology
• Protein Processing, Post-Translational
• Proteostasis
• Ubiquitin-Protein Ligases/metabolism

• R01 HL104129 NHLBI NIH HHS

• Autophagy
• Focal adhesion
• Migration
• NBR1

• Heart failure
• MAPKAPK
• MuRF2
• MuRF3
• Protein homeostasis
• Protein surplus myopathy

• Autophagy
• Receptor regulators
• TRIMs

• Animals
• Disease Models, Animal
• Disease Susceptibility
• Host-Pathogen Interactions
• Humans
• Inflammation/genetics
• Inflammation/pathology
• Inflammation/virology
• Mice
• Phenotype
• Severe acute respiratory syndrome-related coronavirus/genetics
• Severe acute respiratory syndrome-related coronavirus/pathogenicity
• Severe Acute Respiratory Syndrome/genetics
• Severe Acute Respiratory Syndrome/pathology
• Severe Acute Respiratory Syndrome/virology
• Virus Replication/genetics

• U54 AI081680 NIAID NIH HHS
• U01 CA134240 NCI NIH HHS
• U01CA134240 NCI NIH HHS
• U54AI081680 NIAID NIH HHS
• R01 GM070683 NIGMS NIH HHS
• U19 AI100625 NIAID NIH HHS

• murf3
• diabetic cardiomyopathy
• post-translational modification
• multi-ubiquitin
• ppar
• ubiquitin ligase

• Adipose Tissue
• Animals
• Body Composition
• Body Weight
• Diabetic Cardiomyopathies/etiology
• Diabetic Cardiomyopathies/genetics
• Diabetic Cardiomyopathies/metabolism
• Diet, High-Fat/adverse effects
• Heart Failure, Systolic/etiology
• Heart Failure, Systolic/genetics
• Heart Failure, Systolic/metabolism
• In Vitro Techniques
• Mice
• Mice, Knockout
• Muscle Proteins/genetics
• Muscle Proteins/metabolism
• Myocytes, Cardiac/metabolism
• PPAR alpha/metabolism
• PPAR gamma/metabolism
• PPAR-beta/metabolism
• Ubiquitination

• P30 DK056350 NIDDK NIH HHS
• R01 HL104129 NHLBI NIH HHS
• DK056350 NIDDK NIH HHS
• R01HL104129 NHLBI NIH HHS

• MAFbx (Atrogin1)
• MuRF1 (Trim63)
• Muscle RING Finger 1
• Muscle atrophy F-box
• Muscle ubiquitin ligases
• Spinal muscular atrophy (SMA)