Targeting MC1R depalmitoylation to prevent melanomagenesis in redheads

Shuyang Chen, Changpeng Han, Xiao Miao, Xin Li, Chengqian Yin, Junrong Zou, Min Liu, Shanshan Li, Lukasz Stawski, Bo Zhu, Qiong Shi, Zhi-Xiang Xu, Chunying Li, Colin R. Goding (), Jun Zhou () and Rutao Cui ()
Additional contact information
Shuyang Chen: Shandong Normal University
Changpeng Han: Shanghai University of Traditional Chinese Medicine
Xiao Miao: Shanghai University of Traditional Chinese Medicine
Xin Li: Shanghai University of Traditional Chinese Medicine
Chengqian Yin: Boston University School of Medicine
Junrong Zou: Boston University School of Medicine
Min Liu: Shandong Normal University
Shanshan Li: Boston University School of Medicine
Lukasz Stawski: Boston University School of Medicine
Bo Zhu: Boston University School of Medicine
Qiong Shi: The Fourth Military Medical University
Zhi-Xiang Xu: University of Alabama at Birmingham
Chunying Li: The Fourth Military Medical University
Colin R. Goding: University of Oxford
Jun Zhou: Shandong Normal University
Rutao Cui: Boston University School of Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract Some genetic melanocortin-1 receptor (MC1R) variants responsible for human red hair color (RHC-variants) are consequently associated with increased melanoma risk. Although MC1R signaling is critically dependent on its palmitoylation primarily mediated by the ZDHHC13 protein-acyl transferase, whether increasing MC1R palmitoylation represents a viable therapeutic target to limit melanomagenesis in redheads is unknown. Here we identify a specific and efficient in vivo strategy to induce MC1R palmitoylation for therapeutic benefit. We validate the importance of ZDHHC13 to MC1R signaling in vivo by targeted expression of ZDHHC13 in C57BL/6J-MC1RRHC mice and subsequently inhibit melanomagenesis. By identifying APT2 as the MC1R depalmitoylation enzyme, we are able to demonstrate that administration of the selective APT2 inhibitor ML349 treatment efficiently increases MC1R signaling and represses UVB-induced melanomagenesis in vitro and in vivo. Targeting APT2, therefore, represents a preventive/therapeutic strategy to reduce melanoma risk, especially in individuals with red hair.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-08691-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08691-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-08691-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().