The E3 ligase MuRF2 plays a key role in the functional capacity of skeletal muscle fibroblasts

Silvestre, João Guilherme; Baptista, Igor L.; Silva, W.J.; Cruz, André; Silva, M.T.; Miyabara, Elen Haruka; Labeit, Siegfried; Moriscot, Anselmo Sigari

doi:10.1590/1414-431x20198551

Cited by 6 publications

(4 citation statements)

References 40 publications

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“…The integrity of the cytoskeleton and its ability to reorganize rapidly in response to external and internal stimuli is key for normal cell function ( Kaminska et al., 2011 ). It has been reported that E3 ligases can modulate actin cytoskeleton dynamics (reviewed in ( MacGurn et al., 2012 ), these include NEDD4 ( Stawiecka-Mirota et al., 2008 ), MURF2 ( Silvestre et al., 2019 ), RSP5 ( Kaminska et al., 2011 ), OZZ ( Bongiovanni et al., 2012 ), and CLB ( Watanabe et al., 2013 ). Although the role of the ubiquitin-proteasome system in membrane repair via modulation of the cytoskeleton has not been investigated extensively, it has been proposed ( Cai et al., 2009 ; Ibañez-Vega et al., 2019 ; Watanabe et al., 2013 ).…”

Section: Discussionmentioning

confidence: 99%

CHIP-dependent regulation of the actin cytoskeleton is linked to neuronal cell membrane integrity

et al. 2021

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Summary CHIP is an E3-ubiquitin ligase that contributes to healthy aging and has been characterized as neuroprotective. To elucidate dominant CHIP-dependent changes in protein steady-state levels in a patient-derived human neuronal model, CHIP function was ablated using gene-editing and an unbiased proteomic analysis conducted to compare knock-out and wild-type isogenic induced pluripotent stem cell (iPSC)-derived cortical neurons. Rather than a broad effect on protein homeostasis, loss of CHIP function impacted on a focused cohort of proteins from actin cytoskeleton signaling and membrane integrity networks. In support of the proteomics, CHIP knockout cells had enhanced sensitivity to induced membrane damage. We conclude that the major readout of CHIP function in cortical neurons derived from iPSC of a patient with elevate α-synuclein, Parkinson's disease and dementia, is the modulation of substrates involved in maintaining cellular “health”. Thus, regulation of the actin cytoskeletal and membrane integrity likely contributes to the neuroprotective function(s) of CHIP.

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Section: Discussionmentioning

confidence: 99%

CHIP-dependent regulation of the actin cytoskeleton is linked to neuronal cell membrane integrity

et al. 2021

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“…The construct used for screening had high homology between MuRF1 and MuRF2 since both MuRFs share very high homology in their MFC-Bbox-cc segments ( Figure 2 ). Also, the genetic knockdown of MuRF1 has been shown to affect MuRF2 [ 106 , 119 ]. Finally, recent experiments have confirmed that mice with a genetic deletion of MuRF2 do not suffer muscle wasting in cardiac cachexia [ 106 ].…”

Section: Targeted Small-molecule Inhibition Of the E3 Ligase Murf1mentioning

confidence: 99%

Emerging Strategies Targeting Catabolic Muscle Stress Relief

Scalabrin

Adams

Labeit

et al. 2020

IJMS

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Skeletal muscle wasting represents a common trait in many conditions, including aging, cancer, heart failure, immobilization, and critical illness. Loss of muscle mass leads to impaired functional mobility and severely impedes the quality of life. At present, exercise training remains the only proven treatment for muscle atrophy, yet many patients are too ill, frail, bedridden, or neurologically impaired to perform physical exertion. The development of novel therapeutic strategies that can be applied to an in vivo context and attenuate secondary myopathies represents an unmet medical need. This review discusses recent progress in understanding the molecular pathways involved in regulating skeletal muscle wasting with a focus on pro-catabolic factors, in particular, the ubiquitin-proteasome system and its activating muscle-specific E3 ligase RING-finger protein 1 (MuRF1). Mechanistic progress has provided the opportunity to design experimental therapeutic concepts that may affect the ubiquitin-proteasome system and prevent subsequent muscle wasting, with novel advances made in regards to nutritional supplements, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) inhibitors, myostatin antibodies, β2 adrenergic agonists, and small-molecules interfering with MuRF1, which all emerge as a novel in vivo treatment strategies for muscle wasting.

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“…5,6 The function of TRIM55 has been investigated in the development of cardiovascular system and muscle. [7][8][9] Recent reports have established an anti-tumor effect for TRIM55 in cancers. For instance, TRIM55 was found to suppress hepatocellular carcinoma tumorigenesis via regulating EMT and matrix metallopreoteinase-2.…”

Section: Introductionmentioning

confidence: 99%

“…Tripartite motif containing 55 (TRIM55) is an E3 ubiquitin ligase belonging to the TRIM family and is involved in the degradation of a series of crucial proteins 5,6 . The function of TRIM55 has been investigated in the development of cardiovascular system and muscle 7–9 . Recent reports have established an anti‐tumor effect for TRIM55 in cancers.…”

Section: Introductionmentioning

confidence: 99%

TRIM55 inhibits colorectal cancer development via enhancing protein degradation of c‐Myc

Lin¹,

Fang²,

Lin³

et al. 2023

Cancer Medicine

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Background Colorectal cancer (CRC) is one of the most common and lethal malignancies which including colon and rectum cancer. Tripartite motif containing 55 (TRIM55) is an E3 ubiquitin ligase belonging to the TRIM family. Although the aberrant TRIM55 expression has been implicated in several tumors, its functional role, and molecular mechanisms in CRC remain unknown. Methods Immunohistochemical studies, qRT‐PCR, and Western blot were performed to analyze the expression of TRIM55 in CRC patients and cell lines. TRIM55 expression and its relevance to clinical traits and prognosis were further explored in the TCGA database, and in our 87 clinical samples. Subsequently, we performed a series of functional assays to explore the effect of TRIM55 on CRC progression. Finally, the molecular mechanism of TRIM55 was investigated by immunoprecipitation and ubiquitination analyses. Results Here, we demonstrated that TRIM55 was markedly downregulated in CRC cell lines and tumors from CRC patients. Moreover, overexpression of TRIM55 could suppress CRC cell growth in vitro and inhibit CRC xenograft tumor development in vivo. Additionally, TRIM55 overexpression dampened CRC cell migration and invasion. Further bioinformatics analysis indicated that TRIM55 suppressed cyclin D1 and c‐Myc expression. Mechanistically, co‐immunoprecipitation assay revealed that TRIM55 directly interacted with c‐Myc and down‐regulated its protein expression level via protein ubiquitination. Intriguingly, c‐Myc overexpression partially antagonized the function of TRIM55 overexpression. Conclusions Taken together, our findings suggest that TRIM55 inhibits CRC tumor development via, at least in part, enhancing protein degradation of c‐Myc. Targeting TRIM55 could provide a new therapeutic approach for CRC patients.

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The E3 ligase MuRF2 plays a key role in the functional capacity of skeletal muscle fibroblasts

Cited by 6 publications

References 40 publications

CHIP-dependent regulation of the actin cytoskeleton is linked to neuronal cell membrane integrity

CHIP-dependent regulation of the actin cytoskeleton is linked to neuronal cell membrane integrity

Emerging Strategies Targeting Catabolic Muscle Stress Relief

TRIM55 inhibits colorectal cancer development via enhancing protein degradation of c‐Myc

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