A Non-Apoptotic Function for Mcl-1 as an Activator of Canonical Wnt Signaling in Keratinocytes

The study explored a non-apoptotic role of Mcl-1 in keratinocytes, revealing its involvement in activating the canonical Wnt signaling pathway, which is crucial for epidermal morphogenesis. Transgenic mice expressing human Mcl-1 showed increased epidermal thickness and altered keratinocyte differentiation, with some developing benign follicular cysts, indicating Wnt/β-catenin pathway activation. Over-expression of Mcl-1 in human keratinocytes led to increased proliferation and up-regulation of Wnt pathway components, such as β-catenin and c-Myc. The mitogenic activity of Mcl-1 was localized to its N-terminal region, suggesting a novel oncogenic potential beyond its anti-apoptotic function.