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Updated: Jul 14, 2026
09:44
High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
Published on: March 3, 2015
Post-prenylation-processing enzymes as new targets in oncogenesis.
Ann M Winter-Vann1, Patrick J Casey
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Nature Reviews. Cancer
|May 3, 2005
Summary
Targeting post-prenylation processing, specifically isoprenylcysteine carboxyl methyltransferase (ICMT) methylation, offers a promising strategy for controlling cancer cell proliferation, potentially overcoming limitations of prenylation inhibitors.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Oncogenic proteins like RAS undergo prenylation, a critical lipid modification.
- Post-prenylation steps include RCE1 protease processing and ICMT-catalyzed methylation.
- Current prenylation inhibitors show limited efficacy in clinical trials.
Purpose of the Study:
- To investigate the therapeutic potential of inhibiting post-prenylation processing steps.
- To evaluate isoprenylcysteine carboxyl methyltransferase (ICMT) as a drug target for cancer therapy.
Main Methods:
- Analysis of post-translational modifications of oncogenic proteins.
- Evaluation of RCE1 protease and ICMT methyltransferase functions.
- Assessment of cancer cell proliferation in response to targeted inhibition.
Main Results:
- Inhibitors targeting prenylation have shown limited clinical utility.
- Inhibition of ICMT-catalyzed methylation presents a promising alternative strategy.
- Targeting post-prenylation steps may enhance cancer treatment efficacy.
Conclusions:
- ICMT-catalyzed methylation is a critical step in oncogenic protein processing.
- Inhibiting ICMT offers a potentially superior therapeutic approach for cancer treatment.
- Further research into ICMT inhibitors is warranted for cancer therapy development.
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