Comparative Ubiquitinomics of Human Skin Reveals Insulin Receptor Ubiquitination as a Regulator of Collagen Secretion

This study explores the role of ubiquitination in human skin, focusing on its impact on collagen secretion. Researchers analyzed ubiquitination patterns in healthy skin and CYLD cutaneous syndrome (CCS) skin tumors, identifying 1,605 ubiquitin sites across 731 proteins. They found that the most frequent E3 ligase was NEDD4, while USP7 and CYLD were common deubiquitinases. In CCS tumors, 251 sites showed differential ubiquitination, with a focus on cell division and differentiation proteins, including the insulin receptor (INSR). Knockdown of INSR in CCS cells led to reduced secretion of basement membrane proteins, especially COL7A1, suggesting that ubiquitination significantly influences extracellular matrix secretion and tissue architecture.