| First Author | Cao J | Year | 2013 |
| Journal | Mol Cell | Volume | 51 |
| Issue | 4 | Pages | 409-22 |
| PubMed ID | 23973372 | Mgi Jnum | J:203944 |
| Mgi Id | MGI:5529212 | Doi | 10.1016/j.molcel.2013.08.010 |
| Citation | Cao J, et al. (2013) MC1R is a potent regulator of PTEN after UV exposure in melanocytes. Mol Cell 51(4):409-22 |
| abstractText | 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 BRAF(V600E), 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. |
