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Regulation of epidermal differentiation through KDF 1‐mediated deubiquitination of IKK α
Author(s) -
Li Yuanyuan,
Tang Liangfeng,
Yue Jiping,
Gou Xuewen,
Lin Anning,
Weatherbee Scott D,
Wu Xiaoyang
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948566
Subject(s) - microbiology and biotechnology , chemistry , biology
Abstract Progenitor cells at the basal layer of skin epidermis play an essential role in maintaining tissue homeostasis and enhancing wound repair in skin. The proliferation, differentiation, and cell death of epidermal progenitor cells have to be delicately regulated, as deregulation of this process can lead to many skin diseases, including skin cancers. However, the underlying molecular mechanisms involved in skin homeostasis remain poorly defined. In this study, with quantitative proteomics approach, we identified an important interaction between KDF 1 (keratinocyte differentiation factor 1) and IKK α (IκB kinase α) in differentiating skin keratinocytes. Ablation of either KDF 1 or IKK α in mice leads to similar but striking abnormalities in skin development, particularly in skin epidermal differentiation. With biochemical and mouse genetics approach, we further demonstrate that the interaction of IKK α and KDF 1 is essential for epidermal differentiation. To probe deeper into the mechanisms, we find that KDF 1 associates with a deubiquitinating protease USP 7 (ubiquitin‐specific peptidase 7), and KDF 1 can regulate skin differentiation through deubiquitination and stabilization of IKK α. Taken together, our study unravels an important molecular mechanism underlying epidermal differentiation and skin tissue homeostasis.