GSBS Student Publications

Title

Control of cellular senescence by CPEB

Student Author(s)

Maria Ivshina

GSBS Program

Interdisciplinary Graduate Program

UMMS Affiliation

Program in Molecular Medicine

Date

10-4-2006

Document Type

Article

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

Disciplines

Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology | Life Sciences | Medicine and Health Sciences

Abstract

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

10.1101/gad.1438906

Related Resources

Link to article in PubMed

Journal Title

Genes and development

PubMed ID

17015432