IRS-1 phase separation bridges IGF-1R signaling and the MITF/TYR axis to control melanogenesis
Abstract
Melanogenesis is well known to be activated by the α-MSH/MITF signaling pathway. Recent studies have further revealed that the IGF-1/IGF-1R metabolic signaling axis can also induce melanin synthesis. Here, we demonstrate that IRS-1, a key downstream adaptor of both IGF-1R and the insulin receptor (IR), acts as a bridge by connecting the upstream IGF-1R signaling with the downstream MITF/TYR axis to promote melanogenesis. Importantly, this function of IRS-1 may be tissue-specific, as insulin alone fails to stimulate melanogenesis. Deletion of the self-interaction region (SAR) abolishes the phase separation of IRS-1, thereby preventing the activation of melanogenesis. Taken together, our findings reveal a novel function of IRS-1 phase separation in melanogenesis. This work not only sheds light on understanding the regulatory mechanism of melanin homeostasis but also provides a potential strategy for cosmetics companies to develop more effective whitening products.
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BibTeX
@article{liang2026irs1,
title = {{IRS-1 phase separation bridges IGF-1R signaling and the MITF/TYR axis to control melanogenesis}},
author = {Hao Di Liang and Shui Bo Xu and Yi Ting Zhou and Li Ling Zheng and Chien Yi Koay and Hooi Yeen Yap and Bee Leng Lua},
journal = {Frontiers in Molecular Biosciences},
year = {2026},
month = oct,
doi = {10.3389/fmolb.2026.1947504},
url = {https://www.frontiersin.org/articles/10.3389/fmolb.2026.1947504},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - IRS-1 phase separation bridges IGF-1R signaling and the MITF/TYR axis to control melanogenesis
AU - Hao Di Liang
AU - Shui Bo Xu
AU - Yi Ting Zhou
AU - Li Ling Zheng
AU - Chien Yi Koay
AU - Hooi Yeen Yap
AU - Bee Leng Lua
PY - 2026
DA - 2026/10/29
JO - Frontiers in Molecular Biosciences
DO - 10.3389/fmolb.2026.1947504
UR - https://www.frontiersin.org/articles/10.3389/fmolb.2026.1947504
AB - Melanogenesis is well known to be activated by the α-MSH/MITF signaling pathway. Recent studies have further revealed that the IGF-1/IGF-1R metabolic signaling axis can also induce melanin synthesis. Here, we demonstrate that IRS-1, a key downstream adaptor of both IGF-1R and the insulin receptor (IR), acts as a bridge by connecting the upstream IGF-1R signaling with the downstream MITF/TYR axis to promote melanogenesis. Importantly, this function of IRS-1 may be tissue-specific, as insulin alone fails to stimulate melanogenesis. Deletion of the self-interaction region (SAR) abolishes the phase separation of IRS-1, thereby preventing the activation of melanogenesis. Taken together, our findings reveal a novel function of IRS-1 phase separation in melanogenesis. This work not only sheds light on understanding the regulatory mechanism of melanin homeostasis but also provides a potential strategy for cosmetics companies to develop more effective whitening products.
SN - 2296-889X
ER -