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. 2019 Dec 17;47(6):1867–1879. doi: 10.1042/BST20190527

Figure 2. Mechanism of USP8-mediated cortisol hyperproduction in CD.

Figure 2.

14-3-3 proteins fail to bind mutant USP8 leading to cleavage and constitutive activation of USP8. USP8-mediated stabilization and activation of the EGFR ultimately leads to increased transcription of the gene encoding the ACTH precursor proopiomelanocortin (POMC) and the development of corticotroph adenoma. Chronic elevation of ACTH is followed by excessive adrenal glucocorticoid secretion. The stabilization and activation of additional receptor tyrosine kinases, of SMO or deubiquitination of unknown nuclear targets of USP8 may also be involved in enhanced POMC transcription.