MC1R is a potent regulator of PTEN after UV exposure in melanocytes.
Mol Cell
; 51(4): 409-22, 2013 Aug 22.
Article
em En
| MEDLINE
| ID: mdl-23973372
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Raios Ultravioleta
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Melanoma Experimental
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Pigmentação da Pele
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Regulação da Expressão Gênica
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Receptor Tipo 1 de Melanocortina
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PTEN Fosfo-Hidrolase
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Melanócitos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article