Related Experiment Video

Updated: May 15, 2026

Development and Application of Rapamycin-regulated Tyrosine Phosphatases
06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

Disruption of an hTERT-mTOR-RAPTOR protein complex by a phytochemical perillyl alcohol and rapamycin

Tabetha Sundin1, Dennis M Peffley, Patricia Hentosh

  • 1Department of Medical Diagnostic and Translational Sciences, Old Dominion University, 4608 Hampton Blvd., Norfolk, VA 23529, USA.

Molecular and Cellular Biochemistry
|January 4, 2013
PubMed

Insights

Perillyl alcohol and rapamycin reduce prostate cancer cell telomerase activity by disrupting a key protein complex. This post-translational regulation of human telomerase reverse transcriptase (hTERT) involves the mechanistic target of rapamycin (mTOR) pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Telomerase activity is crucial for cancer cell proliferation.
  • Phytochemicals like perillyl alcohol and mTOR inhibitors like rapamycin show potential in cancer therapy.
  • Previous studies indicated perillyl alcohol and rapamycin reduce telomerase activity in prostate cancer cells.

Purpose of the Study:

  • To investigate the post-translational mechanisms by which perillyl alcohol and rapamycin regulate telomerase activity in prostate cancer cells.
  • To determine if a previously identified hTERT-mTOR-S6K-Hsp90-Akt complex exists in prostate cancer cells.
  • To elucidate the role of this complex in the therapeutic effects of perillyl alcohol and rapamycin.

Main Methods:

  • Co-immunoprecipitation assays were used to detect the hTERT complex.
  • Antibodies against RAPTOR or mTOR were employed to capture the complex.
  • Western blotting was used to analyze protein levels and interactions within the complex.

Main Results:

  • A complex involving human telomerase reverse transcriptase (hTERT), mechanistic target of rapamycin (mTOR), S6 kinase (S6K), and Heat shock protein 90 (Hsp90) was confirmed in DU145 prostate cancer cells.
  • Both perillyl alcohol and rapamycin treatment led to the rapid dissociation of this hTERT-mTOR-RAPTOR complex.
  • These agents decreased hTERT protein levels without affecting hTERT mRNA, suggesting post-translational regulation.

Conclusions:

  • The mechanistic target of rapamycin (mTOR) pathway plays a critical role in regulating human telomerase reverse transcriptase (hTERT) in prostate cancer cells.
  • Perillyl alcohol and rapamycin exert their inhibitory effects on telomerase activity by disrupting the hTERT-mTOR complex post-translationally.
  • These findings reveal a novel mechanism of action for perillyl alcohol and rapamycin in prostate cancer, highlighting the mTOR pathway as a therapeutic target.

More Related Videos

A Semi-Quantitative Drug Affinity Responsive Target Stability (DARTS) assay for studying Rapamycin/mTOR interaction05:28

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

Published on: August 27, 2019

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...