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USP14 inhibits autophagy. 42 / 43
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"USP14 is a regulator of de‐ubiquitination and has been reported to be activated through AKT/mTOR pathway and negatively regulate autophagy by K48 de‐ubiquitination in neurodegenerative diseases.32 Hence, we speculated that SPAG5‐AS1 might regulate SPAG5 through USP14.RNA immunoprecipitation analysis confirmed that SPAG5‐AS1 was abundant in USP14‐binding complexes (Figure 6B)."
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"Considering that USP14 negatively regulates autophagy and positively drives NF-κB activation [31, 32], consistent with our observation, we tested the hypothesis in microglial BV2 cells by interfering Usp14 expression (Supplementary Fig. 4a and b; the second one was selected as the most efficient sequence)."
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"SmUCHL5 was expressed at low levels at 10 µM, and research on mammalian cells has shown that the inhibition of UCHL5 and USP14 activates autophagy and apoptosis ( Feng et al., 2014 ; Kim et al., 2018 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Together, it was suggested that SPAG5‐AS1 stabilized SPAG5 protein through interacting with USP14 in HG‐treated HPCs, and that USP14 and AKT/mTOR formed a positive feedback loop.3.7 SPAG5-AS1 promoted apoptosis and attenuated autophagy in HG-treated HPCs through SPAG5/AKT/mTOR pathway."
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"Similarly, 6-Gingerol has been found to inhibit USP14 ubiquitination, enhancing ferritin autophagy and ferroptosis to suppress tumor growth [103]."
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"Typically inhibiting USP14 promotes autophagy in M1 like macrophages and alleviates CLP induced sepsis."
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"Inhibition of USP14 promotes autophagy in M1 macrophages, which reduces the severity of sepsis induced by cecal ligation and puncture (Xu et al., 2020)."
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"Interestingly, it appears USP14 not only negatively regulates the UPS, but also negatively regulates autophagy through removing Lys63 linked ubiquitin chains from the autophagy regulator Beclin-1 [XREF_BIBR]."
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"Accordingly, pharmacological inhibition of USP14 enhanced autophagy and mitophagy in cultured cells [XREF_BIBR, XREF_BIBR, XREF_BIBR], and USP14 knockdown partially reversed the locomotor deficits in PINK1 and Parkin deficient flies [XREF_BIBR]."
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"For example, USP14, known to inhibit protein degradation via the UPS by cleaving the K48-linked ubiquitin chain from the target, could also modulate the autophagy by promoting the K63-linked deubiquitination of specific targets, such as Beclin1."
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"Ubiquitin-specific protease 14 promotes radio-resistance and suppresses autophagy in oral squamous cell carcinoma."
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"USP14 disrupts DDR signaling in autophagy deficient cells."
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"In addition, suppressing USP14 enhanced autophagy in M1-like macrophages and ameliorated cecal ligation and puncture (CLP)-induced sepsis [ 32 ]."
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"In our study, we also found that knockdown of USP14 significantly promoted autophagy in IR-treated OSCC cells, as displayed by the enhanced expression of LC3BII while the reduced p62 expression levels[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Additionally, USP14 knockdown induced autophagy in IR-treated OSCC cells, contributing to the induction of DNA damage and suppression of cell proliferation."
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"The above results indicated that EPI promoted the expression of USP14 by promoting Beclin1 K63 ubiquitination, thereby inhibiting autophagy."
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"On the other hand, it is also possible that the IU1 induced neuroprotection in the post-ischemic mouse brains is a synergistic effect of multiple pathways activated by suppression of USP14 through IU1, since recent results suggest that inhibition of USP14 by IU1 in vitro elevates autophagy activity."
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"Besides, the inhibition of USP14 by IU1-47 induced an increase of the autophagy flux, consistent with the increased degradation rate of Tau [XREF_BIBR]."
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"A previous study has highlighted that USP14 contributed to cell growth, migration, the activation of kinase and inflammasome, as well as inhibited autophagy and apoptosis in cancer cells 14."
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"USP14 has been shown to negatively regulate autophagy, where USP14 KD or inhibition resulted in increased number of autophagy vesicles, autophagosomes, and autolysosomes, increased mitochondrial fragmentation, reduced mitochondrial volume, and increased association between the 20S proteasome and USP14 [84]."
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"Here, USP14 negatively regulated autophagy in a Beclin-1- and Akt-dependent manner."
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"The inhibition of USP14 promotes autophagy, which alleviates DNA damage repair ."
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"Further, USP14 overexpression blocked the autophagy and osteogenic differentiation effects of FOXG1 on BMSCs."
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"According to this observation, it was shown that USP14 suppresses the activity of Beclin1 complex and induction of autophagy by interacting with and controlling K63- rather than K48 linked ubiquitin chains of Beclin1 [XREF_BIBR]."
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"In a previous work, we showed that inhibition of Usp14 enhances the activity of the ubiquitin-proteasome system (UPS), autophagy and mitophagy, and abolishes motor symptoms of two well-established fly models of PD that accumulate dysfunctional mitochondria."
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"Taken together, our results reveal that both downregulation and pharmacological inhibition of Uchl5, as well as Usp14, cause reduction of autophagy."
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"The deubiquitinating enzyme USP14 can negatively regulate autophagy by controlling K63 ubiquitination of Beclin1, and inhibition of USP14 may provide a strategy to promote autophagy [48]."
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"The inhibition of USP14 can promote the autophagy of M1-like macrophages and alleviate sepsis caused by CLP (16)."
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"Therefore, this study has demonstrated that typically inhibiting USP14 promotes autophagy in M1 like macrophages and alleviates CLP induced sepsis."
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"Our data reveal that pharmacological inhibitor treatment of both ubh-4 and usp-14 suppresses autophagy at an early stage.In hypodermal seam cells, b-AP15 treatment did not affect the number of APs but resulted in more ALs (Fig. 6B) suggesting a faster fusion of APs with lysosomes or slow lysosomal degradation."
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"USP14 Suppresses Autophagy by Cleaving Lys63-Ubiquitin Chains from BECLIN 1."
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"Inhibition of USP14 induces ER stress mediated autophagy without apoptosis in lung cancer cell line A549."
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"Deubiquitination of USP14 inhibits autophagy, while ferritin promotes ferroptosis, and autophagy has the ability to regulate ferroptosis through the degradation of ferritin (Mancias et al., 2014; Hou et al., 2016; Xu et al., 2016)."
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"Additionally, an alternative mechanism for the inhibition of autophagy by USP14 has been suggested involving competitive binding of USP14 and Beclin 1 with tumor necrosis factor receptor-associated factor 6 (TRAF6), a downstream effector of the Toll-like receptor 4 (TLR4) signaling, which facilitates the K63-linked ubiquitination of Beclin-1."
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"In addition, it has recently been reported that USP14 negatively regulates autophagy 34, which plays an important role in the regulation of hepatic TG metabolism."
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"We recently reported that inhibition of the deubiquitinating enzyme USP14, which is known to enhance both the UPS and autophagy, increases lifespan and rescues the pathological phenotype of two Drosophila models of PD."
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"Recently, USP14 was found to directly interact with and inhibit the critical autophagy protein BECN1 in a proteasomal independent manner 66."
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"Moreover, we have for the first time demonstrated that the USP14 inhibition induces ER stress mediated autophagy in A549 cells by activation of c-Jun N-terminal kinase 1 (JNK1)."
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"Quantitative global proteomics analysis performed following genetic ablation or pharmacological inhibition of USP14 demonstrated that USP14 loss of function specifically promotes mitochondrial autophagy in iNeurons."
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"In conclusion, the current investigation represents a new mechanism by which inhibition of USP14 triggers autophagy via ER stress mediated UPR in A549 cells."
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"USP14 Negatively Regulates Autophagy Induction."
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"Usp14 knockdown promotes autophagy and diminishes NF-kappaB activation in microglial BV2 cells."
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