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Alternatively spliced forms of cyclin D1 modulate entry into the cell cycle in an inverse manner

H Sawa1, T A Ohshima, H Ukita

  • 1Department of Neurosurgery, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.

Oncogene
|May 15, 1998
PubMed

Insights

Alternative splicing of cyclin D1 gene creates variants that inversely affect cell cycle entry and suppress growth. Overexpression of these cyclin D1 forms upregulates Rb, potentially causing growth inhibition.

Area of Science:

  • Molecular Biology
  • Cell Biology

Background:

  • Alternative splicing of the cyclin D1 gene generates novel mRNA transcripts.
  • These transcripts encode cyclin D1 variants with altered C-terminal domains, excluding exon 5 from the coding sequence.

Purpose of the Study:

  • To investigate the cell cycle regulatory functions of different cyclin D1 splicing variants.
  • To determine the impact of exogenous expression of these variants on cell growth and progression.

Main Methods:

  • Generation of cells expressing distinct cyclin D1 splicing forms.
  • Analysis of cell cycle regulation and growth in response to cyclin D1 variant overexpression.
  • Assessment of Rb gene product levels.

Main Results:

  • Cyclin D1 splicing variants modulated cell cycle entry inversely.
  • Both variants suppressed overall cell growth.
  • Form [a] inhibited S phase entry and completion, while form [b] did not affect G1 to S transition.
  • Overexpression of either form upregulated Rb gene products.

Conclusions:

  • Alternative splicing of cyclin D1 generates functional variants with distinct cell cycle roles.
  • Cyclin D1 variants can suppress cell growth, potentially mediated by Rb upregulation.
  • Understanding these variants is crucial for comprehending cell cycle control and cancer development.

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