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Cyclin-dependent kinase 5 regulates MAPK/ERK signaling in the skin of mice

Xuexian Liu1, Pengqian Zhang2, Kaiyuan Ji1

  • 1College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Mingxian South Road, Taigu 030801, China.

Acta Histochemica
|November 15, 2017
PubMed

Insights

Cyclin-dependent kinase 5 (CDK5) regulates hair color by influencing the mitogen-activated protein kinase (MAPK) pathway. CDK5 knockdown affects MAP3K6, MEK1, and ERK, impacting melanin production.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Cyclin-dependent kinase 5 (CDK5) is a serine/threonine kinase with known roles in various tissues.
  • Previous studies indicated differential CDK5 expression in alpaca skin related to hair color.
  • The precise function of CDK5 in hair color determination remained unclear.

Purpose of the Study:

  • To investigate the functional role of CDK5 in hair color determination.
  • To elucidate the effect of CDK5 on the mitogen-activated protein kinase (MAPK) pathway in mouse skin.
  • To understand the molecular mechanisms linking CDK5 to melanin production.

Main Methods:

  • Construction of CDK5-knockdown mice.
  • Quantitative real-time polymerase chain reaction (qRT-PCR).
  • Co-immunoprecipitation and Western blotting to analyze protein interactions and levels.
  • Analysis of the MAPK pathway components and microRNA expression.

Main Results:

  • CDK5 knockdown altered the MAPK pathway in mouse skin.
  • Phosphorylated CDK5, activated by CDK7, inhibited MAP3K6.
  • This led to decreased MEK1 and ERK expression and increased miR-143-3p, which also targets MAP3K6.
  • MAP3K6 was found to be inhibited in two distinct ways.

Conclusions:

  • CDK5 plays a regulatory role in the MAPK pathway.
  • The findings provide insight into how the MAPK/ERK pathway contributes to the inhibition of melanin production.
  • This mechanism sheds light on the molecular basis of hair color variation.
Keywords:
CDK5CDK5-Knockdown mouseMAP3K6MEK1Pigment

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