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Updated: Jul 31, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Apoptosis signal-regulating kinase 1 (ASK1) is an intracellular inducer of keratinocyte differentiation

K Sayama1, Y Hanakawa, Y Shirakata

  • 1Department of Dermatology, Ehime University School of Medicine, Ehime 791-0295, Japan. sayama@m.ehime-u.ac.jp

The Journal of Biological Chemistry
|October 13, 2000
PubMed

Insights

The ASK1-p38 MAP kinase pathway regulates keratinocyte differentiation. This signaling cascade is crucial for cellular responses to stimuli and is present in human skin.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Dermatology

Background:

  • Cellular differentiation is a fundamental process regulated by intracellular signaling pathways.
  • The mitogen-activated protein (MAP) kinase cascade is a key signal transduction pathway controlling cell fate.
  • Apoptosis signal-regulating kinase 1 (ASK1) is a MAP kinase kinase kinase involved in stress-induced signaling.

Purpose of the Study:

  • To investigate the role of ASK1 in keratinocyte differentiation.
  • To elucidate the involvement of the ASK1-p38 MAP kinase cascade in regulating keratinocyte differentiation markers.

Main Methods:

  • Expression of constitutively active ASK1 (ASK1-DeltaN) in keratinocytes.
  • Analysis of differentiation markers (transglutaminase-1, loricrin, involucrin) and cell cycle.
  • Inhibition of p38 MAP kinase using SB202190 and SB203580.
  • Assessment of ASK1 expression and activity following ceramide-induced differentiation.

Main Results:

  • Constitutively active ASK1 induced keratinocyte differentiation markers and morphological changes.
  • p38 MAP kinase inhibition abolished ASK1-induced differentiation.
  • Ceramide-induced differentiation increased ASK1 expression and activity.
  • ASK1 protein is expressed in the upper epidermis of normal human skin.

Conclusions:

  • The ASK1-p38 MAP kinase cascade is a novel intracellular regulator of keratinocyte differentiation.
  • ASK1 plays a significant role in the in vivo differentiation of keratinocytes.
  • This pathway is implicated in cellular responses to extracellular stimuli.

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