In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 21, No. 10 ( 2017-10), p. 2465-2480
Abstract:
We previously reported that three point mutations in SASH 1 and mutated SASH 1 promote melanocyte migration in dyschromatosis universalis hereditaria ( DUH ) and a novel p53/ POMC /Gαs/ SASH 1 autoregulatory positive feedback loop is regulated by SASH 1 mutations to induce pathological hyperpigmentation phenotype. However, the underlying mechanism of molecular regulation to cause this hyperpigmentation disorder still remains unclear. In this study, we aimed to investigate the molecular mechanism undergirding hyperpigmentation in the dyschromatosis disorder. Our results revealed that SASH 1 binds with MAP 2K2 and is induced by p53‐ POMC ‐ MC 1R signal cascade to enhance the phosphorylation level of ERK 1/2 and CREB . Moreover, increase in phosphorylated ERK 1/2 and CREB levels and melanogenesis‐specific molecules is induced by mutated SASH 1 alleles. Together, our results suggest that a novel SASH 1/ MAP 2K2 crosstalk connects ERK 1/2/ CREB cascade with p53‐ POMC ‐ MC 1R cascade to cause hyperpigmentation phenotype of DUH .
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2017.21.issue-10
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2076114-4