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Differential control of transcription by DNA-bound cyclins

T Y Kim1, W G Kaelin

  • 1Brigham and Womens Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

Molecular Biology of the Cell
|July 14, 2001
PubMed

Insights

Cyclin A acts as a transcriptional repressor, while cyclin E functions as an activator. These distinct roles in gene regulation suggest intrinsic differences in how cyclins modulate transcription when bound to DNA.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Cyclins regulate cell-cycle transitions.
  • Cyclins can associate with DNA-binding proteins.
  • Cyclins possess structural motifs found in transcriptional modulators.

Purpose of the Study:

  • To investigate the transcriptional regulatory potential of cyclin A and cyclin E.
  • To determine if cyclins can directly modulate gene expression.
  • To compare the DNA-binding dependent transcriptional activities of cyclin A and cyclin E.

Main Methods:

  • Utilizing a heterologous DNA-binding domain to tether cyclin A and cyclin E to DNA.
  • Assessing transcriptional activation and repression activities in vitro.
  • Evaluating cell-cycle dependent transcriptional modulation by unfused cyclins at physiological concentrations.

Main Results:

  • Cyclin A functions as a potent transcriptional repressor when tethered to DNA.
  • Cyclin E acts as a potent transcriptional activator when tethered to DNA.
  • Cyclin E, but not cyclin A, activates transcription in a cell-cycle-dependent manner as an unfused protein.

Conclusions:

  • Cyclin A and cyclin E exhibit distinct intrinsic abilities to modulate transcription when associated with DNA.
  • The transcriptional activity of cyclin E is linked to its ability to activate CDK2.
  • These findings highlight differential roles of cyclins in gene expression regulation beyond cell-cycle control.

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