In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 21, No. 4 ( 2017-04), p. 802-815
Abstract:
p53‐Transcriptional‐regulated proteins interact with a large number of other signal transduction pathways in the cell, and a number of positive and negative autoregulatory feedback loops act upon the p53 response. P53 directly controls the POMC /α‐ MSH productions induced by ultraviolet ( UV ) and is associated with UV ‐independent pathological pigmentation. When identifying the causative gene of dyschromatosis universalis hereditaria ( DUH ), we found three mutations encoding amino acid substitutions in the gene SAM and SH 3 domain containing 1 ( SASH 1), and SASH 1 was associated with guanine nucleotide‐binding protein subunit‐alpha isoforms short (Gαs). However, the pathological gene and pathological mechanism of DUH remain unknown for about 90 years. We demonstrate that SASH 1 is physiologically induced by p53 upon UV stimulation and SASH and p53 is reciprocally induced at physiological and pathophysiological conditions. SASH 1 is regulated by a novel p53/ POMC /α‐ MSH /Gαs/ SASH 1 cascade to mediate melanogenesis. A novel p53/ POMC /Gαs/ SASH 1 autoregulatory positive feedback loop is regulated by SASH 1 mutations to induce pathological hyperpigmentation phenotype. Our study demonstrates that a novel p53/ POMC /Gαs/ SASH 1 autoregulatory positive feedback loop is regulated by SASH 1 mutations to induce pathological hyperpigmentation phenotype.
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2017.21.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2076114-4