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Hairless and the polyamine putrescine form a negative regulatory loop in the epidermis
Author(s) -
Luke Courtney T.,
Casta Alexandre,
Kim Hyunmi,
Christiano Angela M.
Publication year - 2013
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.12228
Subject(s) - putrescine , hairless , hair follicle , spermidine , polyamine , biology , spermine , ornithine decarboxylase , microbiology and biotechnology , biochemistry , enzyme
Hairless ( HR ) is a nuclear protein with corepressor activity that is highly expressed in the skin and hair follicle. Mutations in Hairless lead to hair loss accompanied by the appearance of papules (atrichia with papular lesions), and similar phenotypes appear when the key polyamine enzymes ornithine decarboxylase ( ODC ) and spermidine/spermine N 1 ‐acetyltransferase ( SSAT ) are overexpressed. Both ODC and SSAT transgenic mice have elevated epidermal levels of putrescine, leading us to investigate the mechanistic link between putrescine and HR . We show here that HR and putrescine form a negative regulatory network, as epidermal ODC expression is elevated when HR is decreased and vice versa . We also show that the regulation of ODC by HR is dependent on the MYC superfamily of proteins, in particular MYC , MXI 1 and MXD 3. Furthermore, we found that elevated levels of putrescine lead to decreased HR expression, but that the SSAT ‐ TG phenotype is distinct from that found when HR is mutated. Transcriptional microarray analysis of putrescine‐treated primary human keratinocytes demonstrated differential regulation of genes involved in protein–protein interactions, nucleotide binding and transcription factor activity, suggesting that the putrescine‐ HR negative regulatory loop may have a large impact on epidermal homeostasis and hair follicle cycling.

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