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Role of p21 in SP600125-induced cell cycle arrest, endoreduplication, and apoptosis

Dong-Oh Moon1, Yung Hyun Choi, Gi-Young Kim

  • 1Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.

Cellular and Molecular Life Sciences : CMLS
|February 12, 2011
PubMed

Insights

The JNK inhibitor SP600125 activates p21, impacting cell cycle progression and apoptosis. This study reveals p21

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The anti-cancer effects of c-Jun N-terminal kinase (JNK) inhibitor SP600125 are recognized in human cancer cells.
  • The precise role of p21 in SP600125-induced G(2)/M phase distribution remains unclear.

Purpose of the Study:

  • To elucidate the role of p21 in the G(2)/M cell cycle distribution induced by SP600125.
  • To investigate the mechanisms underlying p21 transcriptional activation and its functional consequences.

Main Methods:

  • Investigated SP600125's effects on p21 promoter activity and Sp1 phosphorylation.
  • Utilized inhibitors of ERK, PI3K, and Akt pathways to dissect signaling cascades.
  • Assessed cell cycle distribution, endoreduplication, and apoptosis at specific time points.

Main Results:

  • SP600125 induces transcriptional activation of p21 via ERK-dependent Sp1 phosphorylation.
  • p21 inhibits cyclin E/Cdk2 activity, leading to endoreduplication at 24 hours.
  • SP600125 triggers PI3K/Akt-mediated p21 phosphorylation at Thr 145, conferring anti-apoptotic protection at 48 hours.

Conclusions:

  • p21 exhibits dual functions: inhibiting cell cycle progression at 24 hours and acting as an anti-apoptotic factor at 48 hours.
  • The PI3K/Akt pathway is crucial for SP600125-induced p21 phosphorylation and subsequent apoptosis protection.

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