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The P450 system and mTORC 1 signalling in acne
Author(s) -
Melnik Bodo C.
Publication year - 2014
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12359
Subject(s) - mtorc1 , acne , cytochrome p450 , retinoic acid , chemistry , foxo1 , catabolism , pharmacology , signalling , biochemistry , pi3k/akt/mtor pathway , biology , phosphorylation , signal transduction , microbiology and biotechnology , enzyme , genetics , gene , protein kinase b
In this issue, Hellmann‐Regen et al . suggested that anti‐acne effects of erythromycin and tetracyclines may be related to their inhibitory effect of cytochrome P450‐mediated degradation of all‐trans ‐retinoic acid (ATRA). We have recently proposed that all anti‐acne agents function by attenuation of increased mTORC 1 signalling. This commentary links the P450 system to mTORC 1 regulation in acne. Drug‐mediated induction of P450 activity or P450 mutants with increased catabolic activity may reduce cellular ATRA levels and FoxO1 expression, thus reducing FoxO‐mediated mTORC 1 inhibition. In contrast, agents blocking ATRA degradation such as erythromycin and tetracyclines may improve acne by increasing FoxO1 expression with consecutive inhibition of mTORC 1 signalling.