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. 2019 Sep 4;11(9):1302. doi: 10.3390/cancers11091302

Figure 1.

Figure 1

Ubiquitin-Specific Protease 8 (USP8) hotspot mutations in ACTH-secreting pituitary neuroendocrine tumors (PitNETs). Normally, 14-3-3 proteins bind to the 14-3-3 binding motif (BM) of USP8 Wild-Type (WT) protein when the residue Ser718 is phosphorylated, decreasing USP8 deubiquitinase activity. The most frequent mutations are p.Ser718Pro, p.Ser718del, and p.Pro720Arg, and these mutants completely lose the capability to bind to 14-3-3 proteins. Intriguingly, all these USP8 mutants, after a proteolytic cleavage, generate two fragments. The 40 kDa fragment, or C-fragment, contains the hyperactivated deubiquitinase catalytic domain.