Document Detail


Epiprofin orchestrates epidermal keratinocyte proliferation and differentiation.
MedLine Citation:
PMID:  25344255     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The basal layer of the epidermis contains stem cells and transit amplifying (TA) cells that rapidly proliferate and differentiate further into the upper layers of the epidermis. A number of molecules have been identified as regulators for this process including p63 and Notch1. However, little is known about the mechanisms that regulate the transitions from stem cells to proliferating or differentiating TA cells. Here we demonstrate that Epiprofin (Epfn) plays critical distinct roles in these transition stages as a cell cycle regulator and a transcription factor. Epfn knockout mice have a thickened epidermis, in which p63-expressing basal cells formed multiple layers due to accumulation of premature TA cells with reduced proliferation, and a reduction in differentiating keratinocytes expressing Notch1. We found that low levels of Epfn expression increased proliferation of human immortalized keratinocyte (HaCaT) cells by increasing EGF-responsiveness and superphosphorylation of Rb. In contrast, high levels of Epfn expression promoted cell cycle exit and differentiation, by reducing E2F transactivation and inducing Notch1 expression. Our findings identify multiple novel functions of Epiprofin in epidermal development.
Authors:
Takashi Nakamura; Yasuo Yoshitomi; Kiyoshi Sakai; Vyomesh Patel; Satoshi Fukumoto; Yoshihiko Yamada
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-24
Journal Detail:
Title:  Journal of cell science     Volume:  -     ISSN:  1477-9137     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-25     Completed Date:  -     Revised Date:  2014-10-26    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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