Cyclin-dependent kinase-5 prevents neuronal apoptosis through ERK-mediated upregulation of Bcl-2

C. X. Wang, J. H. Song, D. K. Song, V. W. Yong, A. Shuaib, Chunhai Hao

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Cyclin-dependent kinase-5 (Cdk5) is required for neuronal survival, but its targets in the apoptotic pathways remain unknown. Here, we show that Cdk5 kinase activity prevents neuronal apoptosis through the upregulation of Bcl-2. Treatment of SH-SY5Y cells with retinoid acid (RA) and brain-derived neurotrophic factor (BDNF) generates differentiated neuron-like cells. DNA damage triggers apoptosis in the undifferentiated cells through mitochondrial pathway; however, RA/BDNF treatment results in Bcl-2 upregulation and inhibition of the mitochondrial pathway in the differentiated cells. RA/BDNF treatment activates Cdk5-mediated PI3K/Akt and ERK pathways. Inhibition of Cdk5 inhibits PI3K/Akt and ERK phosphorylation and Bcl-2 expression, and thus sensitizes the differentiated cells to DNA-damage. Inhibition of ERK, but not PI3K/Akt, abrogates Cdk5-medidated Bcl-2 upregulation and the protection of the differentiated cells. This study suggests that ERK-mediated Bcl-2 upregulation contributes to BDNF-induced Cdk5-mediated neuronal survival.

Original languageEnglish (US)
Pages (from-to)1203-1212
Number of pages10
JournalCell Death and Differentiation
Volume13
Issue number7
DOIs
StatePublished - Jul 1 2006
Externally publishedYes

Fingerprint

Cyclin-Dependent Kinase 5
Up-Regulation
Brain-Derived Neurotrophic Factor
Apoptosis
Retinoids
Phosphatidylinositol 3-Kinases
DNA Damage
Acids
Cytoprotection
MAP Kinase Signaling System
Phosphotransferases
Phosphorylation
Neurons

Keywords

  • Apoptosis
  • Bcl-2
  • Cdk5
  • ERK
  • Neurons
  • PI3K

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Cyclin-dependent kinase-5 prevents neuronal apoptosis through ERK-mediated upregulation of Bcl-2. / Wang, C. X.; Song, J. H.; Song, D. K.; Yong, V. W.; Shuaib, A.; Hao, Chunhai.

In: Cell Death and Differentiation, Vol. 13, No. 7, 01.07.2006, p. 1203-1212.

Research output: Contribution to journalArticle

Wang, C. X. ; Song, J. H. ; Song, D. K. ; Yong, V. W. ; Shuaib, A. ; Hao, Chunhai. / Cyclin-dependent kinase-5 prevents neuronal apoptosis through ERK-mediated upregulation of Bcl-2. In: Cell Death and Differentiation. 2006 ; Vol. 13, No. 7. pp. 1203-1212.
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