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Updated: Aug 24, 2026

A Semi-Quantitative Drug Affinity Responsive Target Stability (DARTS) assay for studying Rapamycin/mTOR interaction
05:28

A Semi-Quantitative Drug Affinity Responsive Target Stability (DARTS) assay for studying Rapamycin/mTOR interaction

Published on: August 27, 2019

Evidence for cyclin D3 as a novel target of rapamycin in human T lymphocytes

Marija Hleb1, Shaun Murphy, Eric F Wagner

  • 1Department of Pediatrics, Brown Medical School, Women and Infant's Hospital of Rhode Island, Providence, Rhode Island 02905, USA.

The Journal of Biological Chemistry
|May 8, 2004
PubMed

Insights

Rapamycin, an immunosuppressant, inhibits T cell activation by reducing cyclin D3 levels, a process crucial for cell cycle progression. Overexpressing cyclin D3 makes cells resistant to rapamycin, highlighting its role in immunosuppression.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Rapamycin is an immunosuppressant that inhibits the G1/S transition of the cell cycle.
  • This inhibition is traditionally attributed to p27(Kip1) (p27) and p70 s6 kinase (p70(s6k)) pathways.
  • Recent findings suggest rapamycin's sensitivity persists even without functional p27 or p70(s6k).

Purpose of the Study:

  • To investigate the role of cyclin D3 in rapamycin's immunosuppressive effects.
  • To elucidate the mechanism by which rapamycin affects cell cycle regulators in lymphocytes.

Main Methods:

  • Analyzing cyclin D3 and D2 levels in human T and B lymphocytes treated with rapamycin.
  • Assessing the formation of cyclin D3/CDK complexes and kinase activity.
  • Investigating the transcriptional and translational regulation of cyclin D3.
  • Generating Jurkat T cell transfectants overexpressing cyclin D3 to assess rapamycin resistance.

Main Results:

  • Rapamycin specifically represses cyclin D3 levels in activated human T lymphocytes and B lymphocytes, without affecting cyclin D2.
  • Rapamycin treatment leads to reduced cyclin D3/CDK4/CDK6 complex formation and kinase activity.
  • The decrease in cyclin D3 protein is due to translational repression, not transcriptional changes.
  • Overexpression of cyclin D3 confers resistance to rapamycin in Jurkat T cells.

Conclusions:

  • Cyclin D3 plays a critical role in the immunosuppressive effects of rapamycin on T cells.
  • Rapamycin's regulation of cyclin D3 is a key mechanism for its impact on lymphocyte cell cycle progression.
  • Cyclin D3 is a significant factor in understanding rapamycin's action and general cell cycle regulation in lymphocytes.

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