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OTUB1 activates SLC7A11. 12 / 12
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"Consistent with the data of SLC7A11 mediated by si-OTUB1, the expression of GPX4 was also significantly reduced after OTUB1 knockdown ( Fig. 5 F)."
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"Consistent with the role of a DUB in regulating protein stability, OTUB1 overexpression resulted in reduced SLC7A11 ubiquitination and increased SLC7A11 protein half-life and steady protein levels; conversely, OTUB1 deletion in a variety of cancer cell lines resulted in a significant decrease in SLC7A11 protein levels."
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"As shown in XREF_FIG, the stability of SLC7A11 was effectively rescued by OTUB1 (C91A) but not by OTUB1 (D88A), suggesting that OTUB1 promotes SLC7A11 stabilization independent of its deubiquitinase activity."
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"Taken together, although the precise mechanism by which OTUB1 induces SLC7A11 stabilization requires further elucidation, it is very likely that the binding between OTUB1 and SLC7A11 as well as OTUB1 's ability of inhibiting E2 conjugating enzymes recruited by the unknown E3 ligase contribute to SLC7A11 stabilization induced by OTUB1."
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"For example, in a non neuronal setting, induction of ferroptosis with the small molecule erastin is suppressed by the ubiquitin ligase NEDD4 [XREF_BIBR], whilst the DUBs OTUB1 and USP7 promote ferroptosis by stabilising the mediators SLC7A11 and p53, respectively [XREF_BIBR, XREF_BIBR]."
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"Our research, along with previous studies, indicated that OTUB1 might play a key role in regulating ferroptosis, with the modulation of SLC7A11 by OTUB1 likely being one of the mechanisms by which it inhibits ferroptosis.Ferroptosis, characterized by iron accumulation and lipid peroxidation, plays a critical role in exacerbating immune cell-mediated pathology in SLE and LN [27–30]."
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"A recent study shows that OTUB1 directly interacts with SLC7A11 and prevents SLC7A11 degradation in cancer cells in a TP53-independent manner [ 102 ]."
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"Consequently, the inhibition of OTUB1 or CD44 promotes ferroptotic cancer death through enhancing SLC7A11 degradation, supporting that the critical components along the ubiquitin pathway are a potenti[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In light of the latter findings, future studies addressing whether conditions of diminished GSH levels or increased GSH oxidation affect deubiquitinase S-glutathionylation and implications for their canonical or alternative functions, therefore, appears well warranted.The OTUB1-mediated stabilization of SLC7A11 following its S-glutathionylation depicts a regulatory feed forward mechanism whereby GSH, in a form of a protein-mixed disulfide with OTUB1, regulates its own synthesis in an SLC7A11-dependent manner."
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"Evidence suggests that the deubiquitinase OTUB1, usually overexpressed in cancers, replicates the ferroptosis process and promotes tumor development by stabilizing the cystine transporter SLC7A11 (Gan, 2019)."
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"Lin et al. also concluded that MSC-exos might alleviate ferroptosis via the CD44 and OTUB1-mediated stabilization of SLC7A11 [66]."
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"Solasonine, a steroidal alkaloid, inhibits the expression of transcription factor AP-2 alpha (TFAP2A) and the subsequent transcription of the deubiquitinating enzyme OTUB1, which induces SLC7A11 degra[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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