A muscle-specific UBE2O/AMPKα2 axis promotes insulin resistance and metabolic syndrome in obesity

Vila, Isabelle K.; Park, Mi Kyung; Setijono, Stephanie Rebecca; Yao, Yixin; Kim, Hye-Jin; Badin, Pierre-Marie; Choi, Sekyu; Narkar, Vihang A.; Choi, Sung-Woo; Chung, Jongkyeong; Moro, Cédric; Song, Su Jung; Song, Min Sup

doi:10.1172/jci.insight.128269

Cited by 15 publications

(13 citation statements)

References 72 publications

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“…UBE2O has been reported to play essential roles in cell proliferation and apoptosis, cellular clock function, and metabolic homeostasis [26,[31][32][33]. For instance, UBE2O has been found to control the stability of MLL/COMPASS and play an oncogenic role in MLL-rearranged leukemia [26].…”

Section: Discussionmentioning

confidence: 99%

UBE2O targets Mxi1 for ubiquitination and degradation to promote lung cancer progression and radioresistance

Huang

Yang

et al. 2020

Cell Death Differ

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UBE2O, an E2/E3 hybrid ubiquitin-protein ligase, has been implicated in the regulation of adipogenesis, erythroid differentiation, and tumor proliferation. However, its role in cancer radioresistance remains completely unknown. Here, we uncover that UBE2O interacts and targets Mxi1 for ubiquitination and degradation at the K46 residue. Furthermore, we show that genetical or pharmacological blockade of UBE2O impairs tumor progression and radioresistance in lung cancer in vitro and in vivo, and these effects can be restored by Mxi1 inhibition. Moreover, we demonstrate that UBE2O is overexpressed and negatively correlated with Mxi1 protein levels in lung cancer tissues. Collectively, our work reveals that UBE2O facilitates tumorigenesis and radioresistance by promoting Mxi1 ubiquitination and degradation, suggesting that UBE2O is an attractive radiosensitization target for the treatment of lung cancer.

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Section: Discussionmentioning

confidence: 99%

UBE2O targets Mxi1 for ubiquitination and degradation to promote lung cancer progression and radioresistance

Huang

Yang

et al. 2020

Cell Death Differ

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“…In vitro and in vivo studies showed that overexpression of UBE2O promotes HUVEC function and wound healing, while knockdown of UBE2O impairs function. Previous studies reported that UBE2O ubiquitinates AMPKα2 in skeletal muscle cells and tumor cells [25,26]. Using the tissue-specific PPI network analysis, sixteen genes were identified as targets of UBE2O on skin tissue.…”

Section: Discussionmentioning

confidence: 99%

Saliva exosomes-derived UBE2O mRNA promotes angiogenesis in cutaneous wounds by targeting SMAD6

Chen

Xiong

et al. 2020

J Nanobiotechnol

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Background: Enhancing angiogenesis is critical for accelerating wound healing. Application of different types of exosomes (Exos) to promote angiogenesis represents a novel strategy for enhanced wound repair. Saliva is known to accelerate wound healing, but the underlying mechanisms remain unclear. Results: Our results have demonstrated that saliva-derived exosomes (saliva-Exos) induce human umbilical vein endothelial cells (HUVEC) proliferation, migration, and angiogenesis in vitro, and promote cutaneous wound healing in vivo. Further experiments documented that Ubiquitin-conjugating enzyme E2O (UBE2O) is one of the main mRNAs of saliva-Exos, and activation of UBE2O has effects similar to those of saliva-Exos, both in vitro and in vivo. Mechanistically, UBE2O decreases the level of SMAD family member 6 (SMAD6), thereby activating bone morphogenetic protein 2 (BMP2), which, in turn, induces angiogenesis. Conclusions: The present work suggests that administration of saliva-Exos and UBE2O represents a promising strategy for enhancing wound healing through promotion of angiogenesis.

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“…Previous studies reported that UBE2O ubiquitinates AMPKα2 in skeletal muscle cells and tumor cells. [25,26] Using the tissue-specific PPI network analysis, sixteen genes were identified as targets of UBE2O on skin tissue. Previous studies reported that UBE2O can target SMAD6 during bone morphogenetic protein signaling, [13] but its role in wound healing has yet to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Saliva Exosomes-Derived UBE2O Promotes Angiogenesis in Cutaneous Wounds By Targeting SMAD6

Chen

Xiong

et al. 2020

SSRN Journal

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A muscle-specific UBE2O/AMPKα2 axis promotes insulin resistance and metabolic syndrome in obesity

Cited by 15 publications

References 72 publications

UBE2O targets Mxi1 for ubiquitination and degradation to promote lung cancer progression and radioresistance

UBE2O targets Mxi1 for ubiquitination and degradation to promote lung cancer progression and radioresistance

Saliva exosomes-derived UBE2O mRNA promotes angiogenesis in cutaneous wounds by targeting SMAD6

Saliva Exosomes-Derived UBE2O Promotes Angiogenesis in Cutaneous Wounds By Targeting SMAD6

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