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 keratinocyte proliferation, along with altered differentiation marker expression, indicating Wnt pathway activation. Over-expression of Mcl-1 in human keratinocytes led to increased β-catenin and other Wnt pathway components, promoting cell proliferation. The mitogenic activity was localized to the N-terminal region of Mcl-1. This function of Mcl-1 suggested a novel, potentially oncogenic role beyond its known anti-apoptotic activity.