APOBEC3 regulates keratinocyte differentiation and expression of Notch3
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Updated: Jan 21, 2026

Characterization of In Vitro Differentiation of Human Primary Keratinocytes by RNA-Seq Analysis
Published on: May 16, 2020
Teruki Dainichi1, Yuri Nakano1, Kousho Wakae2
1Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Abstract:
Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family consists of deaminases. Some isozymes of APOBEC3 are induced upon human papillomavirus infection or development of psoriasis skin lesions. However, the involvement of APOBEC3 in keratinocyte differentiation has not been addressed. We herein sought to evaluate the roles of APOBECs in mouse primary keratinocyte differentiation. We found that expression levels of APOBEC1 and APOBEC3 were increased during calcium-induced keratinocyte differentiation. Unexpectedly, however, the expression levels of keratinocyte differentiation markers keratin 1/10, involucrin, loricrin and filaggrin were higher in keratinocytes treated with APOBEC3 siRNAs than in those treated with control RNAs. In addition, the treatment of keratinocytes with APOBEC3 siRNAs increased the gene expression levels of Notch3, a master regulator of keratinocyte differentiation. Moreover, calcium-induced increase in Notch3 expression and keratinocyte differentiation were impaired by transfection with an APOBEC3 expression plasmid. Furthermore, co-treatment with Notch3 siRNAs reduced the APOBEC3 siRNA-mediated upregulation of Notch3 expression and in part attenuated the increased expression levels of keratinocyte differentiation markers. These results suggest that APOBEC3 is induced upon keratinocyte differentiation and negatively regulates the keratinocyte differentiation in part by its inhibitory role for Notch3 expression.
Insights
Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) is induced during keratinocyte differentiation but inhibits this process. APOBEC3 negatively regulates keratinocyte differentiation, partly by suppressing Notch3 expression.
Area of Science:
- Biochemistry
- Molecular Biology
- Dermatology
Background:
- The Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family comprises deaminases.
- APOBEC3 isozymes are implicated in viral infections and skin conditions like psoriasis.
- The role of APOBEC3 in keratinocyte differentiation remains unexplored.
Purpose of the Study:
- To investigate the function of APOBECs in mouse primary keratinocyte differentiation.
- To elucidate the regulatory relationship between APOBEC3 and keratinocyte differentiation markers.
- To determine the involvement of Notch3 signaling in APOBEC3-mediated keratinocyte differentiation.
Main Methods:
- Calcium-induced differentiation of mouse primary keratinocytes.
- RNA interference (siRNA) to knockdown APOBEC3 expression.
- Quantitative gene expression analysis of differentiation markers and Notch3.
- Overexpression of APOBEC3 and co-treatment with Notch3 siRNA.
Main Results:
- APOBEC1 and APOBEC3 expression increased during keratinocyte differentiation.
- APOBEC3 knockdown enhanced the expression of keratinocyte differentiation markers (keratin 1/10, involucrin, loricrin, filaggrin).
- APOBEC3 knockdown upregulated Notch3 expression, a key regulator of keratinocyte differentiation. APOBEC3 overexpression impaired Notch3 induction and differentiation. Notch3 knockdown partially reversed APOBEC3 siRNA effects.
Conclusions:
- APOBEC3 is induced during keratinocyte differentiation.
- APOBEC3 negatively regulates keratinocyte differentiation.
- APOBEC3 exerts its inhibitory effect, in part, through suppressing Notch3 expression.
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