Control of cellular senescence by CPEB
Irina Groisman1, Maria Ivshina, Veronica Marin
1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Genes & Development
|October 4, 2006
Summary
Cytoplasmic polyadenylation element-binding protein (CPEB) controls cellular senescence by repressing myc translation. Loss of CPEB leads to immortal cells, while its presence induces senescence.
Area of Science:
- Molecular Biology
- Cellular Biology
- Cancer Research
Background:
- Cytoplasmic polyadenylation element-binding protein (CPEB) is an RNA-binding protein regulating translation.
- Cellular senescence is a crucial tumor-suppressive mechanism.
- CPEB's role in senescence has not been fully elucidated.
Purpose of the Study:
- To investigate the function of CPEB in cellular senescence.
- To determine the molecular mechanisms by which CPEB influences senescence.
- To identify CPEB targets involved in senescence regulation.
Main Methods:
- Utilized CPEB knockout (KO) mouse embryo fibroblasts (MEFs) and wild-type MEFs.
- Assessed senescence entry and immortality in cultured MEFs.
- Investigated the effect of exogenous CPEB and the role of tumor suppressors (p53, p19ARF, p16INK4A) and Ras.
- Analyzed myc mRNA translation and expression levels.
Main Results:
- CPEB KO MEFs are immortal and bypass senescence, unlike wild-type MEFs.
- Exogenous CPEB restores senescence in KO MEFs and induces precocious senescence in wild-type MEFs.
- CPEB's senescence-inducing function is dependent on p53, p19ARF, and p16INK4A.
- Ras-induced senescence is impaired in CPEB-deficient MEFs, suggesting CPEB acts downstream of Ras.
- Unregulated myc mRNA translation in KO MEFs correlates with senescence bypass.
Conclusions:
- CPEB acts as a translational repressor, specifically inhibiting myc mRNA translation.
- CPEB plays a critical role in promoting cellular senescence, likely through repression of oncogenic translation.
- Dysregulation of CPEB may contribute to cellular immortalization and potentially cancer development.
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