Regulation of airway smooth muscle cyclin D1 transcription by protein kinase C-delta

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Updated: Sep 30, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Kristen Page1, Jing Li, Kevin C Corbit

  • 1Department of Pediatrics and the Ben May Institute for Cancer Research, University of Chicago, Chicago, Illinois, USA.

American Journal of Respiratory Cell and Molecular Biology
|August 2, 2002
PubMed

Insights

Protein kinase C-delta (PKCdelta) inhibits cell cycle progression by regulating cyclin D1 transcription. PKCdelta impacts CRE/ATF2, NF-kappaB, and Ets regulatory elements to control cyclin D1 gene expression.

Area of Science:

  • Molecular biology
  • Cell signaling
  • Gene regulation

Background:

  • Protein kinase C-delta (PKCdelta) is implicated in cell cycle control, but its precise inhibitory mechanism remains unclear.
  • Cyclin D1 is a key regulator of cell cycle progression, and its transcription is influenced by various signaling pathways.

Purpose of the Study:

  • To elucidate the mechanism by which PKCdelta regulates cyclin D1 transcription in airway smooth muscle cells.
  • To identify the specific cis-acting regulatory elements and transcription factors involved in PKCdelta-mediated control of the cyclin D1 promoter.

Main Methods:

  • Overexpression of active and dominant-negative PKCdelta mutants in primary bovine airway smooth muscle cells.
  • Reporter assays using cyclin D1 promoter constructs with 5' deletions and site mutations.
  • Electrophoretic mobility gel shift assays (EMSA) and reporter assays to assess transcription factor binding and activity.

Main Results:

  • PKCdelta overexpression attenuated platelet-derived growth factor (PDGF)-mediated cyclin D1 promoter activity.
  • The CRE/ATF2 site acted as a PDGF enhancer, while the NF-kappaB site functioned as a suppressor.
  • PKCdelta inhibited CRE/ATF2 binding and transactivation, activated NF-kappaB binding and transactivation, and attenuated Ets transactivation.

Conclusions:

  • PKCdelta negatively regulates cyclin D1 transcription through modulation of multiple cis-acting elements.
  • These findings reveal a novel mechanism for PKCdelta in controlling cell cycle progression via cyclin D1 gene expression.

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