Control of cellular senescence by CPEB
Interdisciplinary Graduate Program
Program in Molecular Medicine
Medical Subject Headings
Animals; Blotting, Western; Cell Aging; Cell Cycle; Cell Cycle Proteins; Cells, Cultured; Cyclin-Dependent Kinase Inhibitor p16; Fibroblasts; Male; Mice; Mice, Knockout; Phosphorylation; Protein Binding; Protein Biosynthesis; Proto-Oncogene Proteins c-myc; RNA, Messenger; RNA-Binding Proteins; Tumor Suppressor Protein p14ARF; Tumor Suppressor Protein p53; mRNA Cleavage and Polyadenylation Factors
Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology | Life Sciences | Medicine and Health Sciences
Cytoplasmic polyadenylation element-binding protein (CPEB) is a sequence-specific RNA-binding protein that promotes polyadenylation-induced translation. While a CPEB knockout (KO) mouse is sterile but overtly normal, embryo fibroblasts derived from this mouse (MEFs) do not enter senescence in culture as do wild-type MEFs, but instead are immortal. Exogenous CPEB restores senescence in the KO MEFs and also induces precocious senescence in wild-type MEFs. CPEB cannot stimulate senescence in MEFs lacking the tumor suppressors p53, p19ARF, or p16(INK4A); however, the mRNAs encoding these proteins are unlikely targets of CPEB since their expression is the same in wild-type and KO MEFs. Conversely, Ras cannot induce senescence in MEFs lacking CPEB, suggesting that it may lie upstream of CPEB. One target of CPEB regulation is myc mRNA, whose unregulated translation in the KO MEFs may cause them to bypass senescence. Thus, CPEB appears to act as a translational repressor protein to control myc translation and resulting cellular senescence.
Rights and Permissions
Citation: Genes Dev. 2006 Oct 1;20(19):2701-12. Link to article on publisher's site
DOI of Published Version
Genes and development
Groisman, Irina; Ivshina, Maria; Marin, Veronica; Kennedy, Norman J.; Davis, Roger J.; and Richter, Joel D., "Control of cellular senescence by CPEB" (2006). GSBS Student Publications. 418.