MC1R is a potent regulator of PTEN after UV exposure in melanocytes

Juxiang Cao, Lixin Wan, Elke Hacker, Xiangpeng Dai, Stefania Lenna, Celia Jimenez-Cervantes, Yongjun Wang, NickR Leslie, GeorgeX Xu, HansR Widlund, Byungwoo Ryu, RhodaM Alani, Ken Dutton-Regester, ColinR Goding, NicholasK Hayward, Wenyi Wei, Rutao Cui

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)409-422
Number of pages14
JournalMolecular Cell
Volume51
Issue number4
DOIs
StatePublished - Aug 22 2013
Externally publishedYes

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Receptor, Melanocortin, Type 1
Melanocytes
Phosphoric Monoester Hydrolases
Phosphatidylinositol 3-Kinases
Hair Color
Tanning
Tensins
Melanoma
Skin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Cao, J., Wan, L., Hacker, E., Dai, X., Lenna, S., Jimenez-Cervantes, C., ... Cui, R. (2013). MC1R is a potent regulator of PTEN after UV exposure in melanocytes. Molecular Cell, 51(4), 409-422. https://doi.org/10.1016/j.molcel.2013.08.010

MC1R is a potent regulator of PTEN after UV exposure in melanocytes. / Cao, Juxiang; Wan, Lixin; Hacker, Elke; Dai, Xiangpeng; Lenna, Stefania; Jimenez-Cervantes, Celia; Wang, Yongjun; Leslie, NickR; Xu, GeorgeX; Widlund, HansR; Ryu, Byungwoo; Alani, RhodaM; Dutton-Regester, Ken; Goding, ColinR; Hayward, NicholasK; Wei, Wenyi; Cui, Rutao.

In: Molecular Cell, Vol. 51, No. 4, 22.08.2013, p. 409-422.

Research output: Contribution to journalArticle

Cao, J, Wan, L, Hacker, E, Dai, X, Lenna, S, Jimenez-Cervantes, C, Wang, Y, Leslie, N, Xu, G, Widlund, H, Ryu, B, Alani, R, Dutton-Regester, K, Goding, C, Hayward, N, Wei, W & Cui, R 2013, 'MC1R is a potent regulator of PTEN after UV exposure in melanocytes', Molecular Cell, vol. 51, no. 4, pp. 409-422. https://doi.org/10.1016/j.molcel.2013.08.010
Cao J, Wan L, Hacker E, Dai X, Lenna S, Jimenez-Cervantes C et al. MC1R is a potent regulator of PTEN after UV exposure in melanocytes. Molecular Cell. 2013 Aug 22;51(4):409-422. https://doi.org/10.1016/j.molcel.2013.08.010
Cao, Juxiang ; Wan, Lixin ; Hacker, Elke ; Dai, Xiangpeng ; Lenna, Stefania ; Jimenez-Cervantes, Celia ; Wang, Yongjun ; Leslie, NickR ; Xu, GeorgeX ; Widlund, HansR ; Ryu, Byungwoo ; Alani, RhodaM ; Dutton-Regester, Ken ; Goding, ColinR ; Hayward, NicholasK ; Wei, Wenyi ; Cui, Rutao. / MC1R is a potent regulator of PTEN after UV exposure in melanocytes. In: Molecular Cell. 2013 ; Vol. 51, No. 4. pp. 409-422.
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AU - Lenna, Stefania

AU - Jimenez-Cervantes, Celia

AU - Wang, Yongjun

AU - Leslie, NickR

AU - Xu, GeorgeX

AU - Widlund, HansR

AU - Ryu, Byungwoo

AU - Alani, RhodaM

AU - Dutton-Regester, Ken

AU - Goding, ColinR

AU - Hayward, NicholasK

AU - Wei, Wenyi

AU - Cui, Rutao

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