APOBEC3 regulates keratinocyte differentiation and expression of Notch3

Teruki Dainichi1, Yuri Nakano1, Kousho Wakae2

  • 1Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Experimental Dermatology
|August 11, 2019
PubMed

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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