The Department of Molecular and Cell Biology presents faculty candidate, Rutao Cui, M.D., Ph.D. from Boston University.
Presentation Title: MC1R Is a Potent Regulator of PTEN after UV Exposure in Melanocytes
The individuals carrying melanocortin-1 receptor (MC1R) variants, especially those associated with red hair color, fair skin, and poor tanning ability (RHC trait), are more prone to melanoma; however, the underlying mechanism is poorly defined. Here, we report that UVB exposure triggers phosphatase and tensin homolog (PTEN) interaction with wild-type (WT), but not RHC-associated MC1R variants, which protects PTEN from WWP2-mediated degradation, leading to AKT inactivation.
Strikingly, the biological consequences of the failure of MC1R variants to suppress PI3K/AKT signaling are highly context dependent. In primary melanocytes, hyperactivation of PI3K/AKT signaling leads to premature senescence; in the presence of BRAFV600E, MC1R deficiency-induced elevated PI3K/AKT signaling drives oncogenic transformation. These studies establish the MC1R-PTEN axis as a central regulator for melanocytes response to UVB exposure and reveal the molecular basis underlying the association between MC1R variants and melanomagenesis.
Refreshments will be served at 3:45 p.m. in Suite FO3.606