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p27 suppresses cyclooxygenase-2 expression by inhibiting p38β and p38δ-mediated CREB phosphorylation upon arsenite

Xun Che1, Jinyi Liu, Haishan Huang

  • 1Nelson Institute of Environmental Medicine, New York University, School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA.

Biochimica Et Biophysica Acta
|May 4, 2013
PubMed

Insights

The tumor suppressor p27 inhibits cyclooxygenase-2 (COX-2) expression via p38β/δ-mediated CREB phosphorylation, revealing a novel CDK-independent cancer suppression mechanism.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Cycle Regulation

Background:

  • p27 is a cyclin-dependent kinase (CDK) inhibitor and tumor suppressor.
  • p27 regulates cell cycle G0 to S phase transition.
  • Novel CDK-independent functions of p27 are being investigated.

Purpose of the Study:

  • To elucidate novel mechanisms of p27 tumor suppression.
  • To investigate the role of p27 in regulating cyclooxygenase-2 (COX-2) expression.
  • To identify molecular pathways involved in p27's CDK-independent functions.

Main Methods:

  • Investigated p27-deficiency (p27-/-) and p27 introduction effects on COX-2 expression.
  • Analyzed transcriptional regulation of COX-2.
  • Identified key signaling pathways including p38β, p38δ, and CREB phosphorylation.

Main Results:

  • p27 deficiency elevates COX-2 expression transcriptionally.
  • p27 introduction restores COX-2 expression to normal levels.
  • p27 inhibits COX-2 via p38β/δ-mediated phosphorylation of CREB.

Conclusions:

  • p27 exhibits a novel tumor suppressive role through CDK-independent inhibition of COX-2.
  • The p38β/δ-CREB pathway is critical for p27's regulation of COX-2.
  • These findings expand the understanding of p27's multifaceted tumor suppressor functions.

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