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OTUD5 activates SYNM. 11 / 11
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"Furthermore, confocal microscopic analysis visualized that the co‐localization of α‐Syn and LAMP1, a marker of lysosomes, was significantly enhanced by OTUD5 overexpression (Figure 2B)."
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"In contrast, a pronounced reduction in TH levels induced by α‐Syn PFF was rescued by OTUD5 overexpression in SH‐SY5Y cells (Figure S13B Supporting Information)."
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"35 Interestingly, the degradation of endogenous α‐Syn induced by OTUD5 was evidently blocked by CQ, but not MG132 or 3‐MA (Figure  2A)."
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"We then defined the type of polyubiquitin chains attached to α‐Syn mediated by OTUD5."
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"19 , 41 Therefore, we investigated whether the degradation of α‐Syn mediated by OTUD5 relied on NEDD4."
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"Firstly, we transfected siRNA specific to human NEDD4 into SH‐SY5Y cells and found that NEDD4 knockdown mitigated the degradation of α‐Syn induced by OTUD5 overexpression (Figure  4A)."
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"In contrast, OTUD5 knockout in HEK293T cells impaired the binding of NEDD4 and α‐Syn (Figure 4H)."
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"42 To validate our hypothesis that OTUD5 may recruit NEDD4 to degrade α‐Syn, we first demonstrated that OTUD5 failed to enhance the degradation of α‐Syn when NEDD4 was knockdown, while NEDD4 overexpression promoted the degradation of α‐Syn induced by OTUD5, which indicated that OTUD5 mediated α‐Syn degradation relying on NEDD4."
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"Our results showed that the degradation of α‐Syn induced by OTUD5 changed rarely in ATG5 knockout cells (Figure 2C)."
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"These data indicated that the degradation of α‐Syn induced by OTUD5 may not occur through autophagy‐lysosomal pathway."
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"To further explore how OTUD5 promoted α‐Syn degradation, we examined whether OTUD5 interacted with α‐Syn."
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