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UCHL1 activates AKT. 17 / 20
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"Previous studies have shown that UCHL1 leads to the activation of AKT, as evidenced by the upregulation of phosphorylated AKT.39–43 Likewise, our results showed that UCHL1 deficiency decreased the phosphorylation level of AKT in macrophages."
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"Whether UCH-L1 activates upstream signaling of Akt needs further study."
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"UCH-L1 promotes the metastasis of gastric cancer cells by up-regulating protein kinase B (Akt) and extracellular signal-regulated kinases (ERK1/2), and by constructing a mouse model of lung metastasis, it was found that upregulation of hypoxia-inducible factor-1α (HIF-1α) activity promoted the metastasis of breast cancer cells and lung cancer cells [33,34]."
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"While UCH-L1 has been shown to inhibit alpha 2 -adrenergic receptor (AR) agonist mediated activation of ERK via a direct association with alpha 2A -AR receptor implicating a role of UCH-L1 in neuro-protection XREF_BIBR, it has also been documented that UCH-L1 up-regulates oncogenic beta-catenin and TCF and Akt signaling to induce tumor cell proliferation and migration contributing to tumor progression XREF_BIBR, XREF_BIBR."
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"Together, these data suggest UCH-L1 elicits at least some of its cellular effects through Akt dependent signaling and that stimulation of Akt by UCH-L1 is a potential mechanism of UCH-L1-mediated oncogenesis (XREF_FIG)."
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"Since UCH-L1 has been described to increase AKT activity through inhibition of PHLPP1 phosphatase in tumor cells of UCH-L1 transgenic mice [31] , we evaluated the phosphorylation status of p27 Kip1 at[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Nevertheless, stimulation of Akt by UCH-L1 and the subsequent promotion of prosurvival signaling may contribute to the function of UCH-L1 in oncogenesis."
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"Additionally, it might be possible that activation of Akt signaling by UCH-L1 [XREF_BIBR, XREF_BIBR] might also contribute to its control over p53, as Akt is an established negative regulator of p53 activity [XREF_BIBR, XREF_BIBR]."
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"UCHL1 activated Akt and Erk1/2, which process also required enzymatic activity and was necessary for mediating cell migration and invasion."
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"Whether UCH-L1 activates upstream signaling of Akt needs further study."
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"UCHL1 activated Akt and Erk1/2, which process also required enzymatic activity and was necessary for mediating cell migration and invasion."
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"These findings demonstrated that UCHL1 promoted cell proliferation, migration, and invasion depending on its de-ubiquitinase activity by activating Akt and Erk1/2, which may account for its higher positive expression rate in liver metastases from gastric cancer."
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"Finally, we demonstrated that overexpression of UCH-L1 led to activation of Akt as evidenced by upregulation of phosphorylated Akt."
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"Moreover, UCHL1 smKO increased Akt and Pink1/Parkin activities."
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"Moreover, UCHL1-mediated activation of the AKT and MAPK signaling pathways phosphorylates mouse double minute 2 (MDM2), which results in p53 downregulation."
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"Moreover, we observed that UCHL1 promoted the degradation of p110alpha through autophagy, but paradoxically increased the activity of AKT, thereby promoting polarization of macrophages into pro-inflammatory states."
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"Similarly, the deubiquitinating enzyme UCHL1 has been shown to enhance AKT pathway activation by suppressing the levels of PHLPP1 an effect found to drive the development of lymphoma in vivo [206]."
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