Regulation of MITF stability by the USP13 deubiquitinase

摘要: The microphthalmia-associated transcription factor (MITF) is essential for melanocyte development. Mutation-induced MAPK pathway activation common in melanoma and induces MITF phosphorylation, ubiquitination, proteolysis. Little known about the enzymes involved ubiquitination/deubiquitination. Here we report identification of a deubiquitinating enzyme, named ubiquitin-specific protease 13 (USP13) that appears to be responsible deubiquitination, utilizing short hairpin RNA library against enzymes. Through USP13 stabilizes upregulates protein levels. Conversely, suppression (through knockdown) leads dramatic loss protein, but not messenger RNA. its effects on was observed modulate expression downstream target genes and, thereby, growth soft agar nude mice. These observations suggest as potentially drugable protease, might viable therapeutic melanoma.