In melanoma and colorectal cell lines, deletion of USP15 induces MDM2 auto-ubiquitination and degradation and USP15 negatively regulates the T-cell transcription factor NFATc2 by decreasing MDM2 auto-ubiquitination and degradation, thereby inhibiting T-cell proliferation and activation (Fig. 2C).35 This evidence concerns the gene USP15 and melanoma.