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UCHL1 activates HIF1. 17 / 19
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"Because HIF-1 activity is known to be regulated at multiple steps, we first aimed to identify the key regulatory mechanism in the UCHL1 mediated activation of HIF-1 in EMT6 cells."
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"The inhibitor of UCHL1 , LDN-57444 ( Figure 6J ) , blocks the UCHL1-HIF1 axis and therefore inhibits HIF-1 activity as UCHL1 deubiquitinate and stabilizes HIF-1alpha ."
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"In the present study, we provided direct evidence to show that UCHL1 was responsible for the deubiquitination of HIF-1alpha and upregulated HIF-1 activity."
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"Using an elegant screening approach to identify factors that would lead to HIF-1 transcriptional activity under normoxic conditions, Goto et al. recently identified the ubiquitin C-terminal hydrolase-L1 (UCHL1) as a HIF-1 deubiquitinating enzyme that promotes HIF-1 activity under normoxic and hypoxic conditions by preventing VHL mediated degradation of HIF-1 (XREF_FIG)."
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"The forced expression of UCHL1 significantly enhanced HIF-1 activity regardless of the oxygen conditions."
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"These results clearly indicated that UCHL1 upregulated HIF-1 activity in various cancer cell lines."
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"First, we performed a luciferase assay using the 5HRE-luc reporter gene 43, which expresses luciferase bioluminescence in a HIF-1-dependent manner, in order to test whether UCHL1 enhanced HIF-1 activity in EMT6 cells."
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"UCHL1 deubiquitinates HIF-1alpha protein [ 31 ] , upregulates HIF-1 activity , and mediates cellular protection under hypoxia ."
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"The inhibitor of UCHL1, LDN-57444 (XREF_FIG J), blocks the UCHL1-HIF1 axis and therefore inhibits HIF-1 activity as UCHL1 deubiquitinate and stabilizes HIF-1alpha."
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"These results suggested that the expression of UCHL1 would lead to a poor prognosis by activating HIF-1; therefore, it could be a useful prognostic marker."
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"We then examined the molecular mechanisms underlying the upregulation of HIF-1 by UCHL1."
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"In order to fully elucidate the molecular mechanisms underlying the UCHL1 mediated upregulation of HIF-1 activity, further investigation is needed."
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"We performed a luciferase assay using the 5HREp-luc reporter gene, which expressed firefly luciferase under the control of 5HREp XREF_BIBR XREF_BIBR, to examine whether UCHL1 induced HIF-1 activity."
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"These results collectively indicate that UCHL1 stabilizes HIF-1alpha protein, and elicits HIF-1 activity in a deubiquitinating activity dependent manner in EMT6 cells."
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"We subsequently investigated the influence of the UCHL1 mediated activation of HIF-1 on tumour malignancy."
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"UCHL1 upregulates HIF-1 activity."
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"In the present study, we found that the UCHL1 mediated activation of HIF-1 through the deubiquitination of HIF-1alpha protein induced the antioxidant and radioresistant properties of cancer cells by producing an antioxidant, GSH, through the so called carbohydrate metabolic reprogramming and subsequent activation of the pentose phosphate pathway."
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