Figure 3. Cushing’s disease-associated mutations of USP8 release the autoinhibition of USP8 (IMAGE)

Tokyo Institute of Technology

Figure 3. Cushing’s disease-associated mutations of USP8 release the autoinhibition of USP8

Caption

Wildtype USP8 activity is regulated by the adaptor protein 14-3-3. 14-3-3 inhibits USP8 in part through the enhancement of the interaction of the WW-like domain and the catalytic domain (USP domain in the figure). The mutation hotspot in Cushing’s disease is located on the 14-3-3-binding motif in USP8. The mutations render USP8 unable to bind to 14-3-3, which, in turn, suppresses the interaction of the WW-like and catalytic domains, causing constitutive activation of USP8 and Cushing’s disease pathogenesis

Credit

Communications Biology

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