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Competition of CUGBP1 and calreticulin for the regulation of p21 translation determines cell fate
Author(s) -
Iakova Polina,
Wang GuoLi,
Timchenko Lubov,
Michalak Marek,
PereiraSmith Olivia M,
Smith James R,
Timchenko Nikolai A
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600052
Subject(s) - biology , translation (biology) , calreticulin , rna binding protein , microbiology and biotechnology , messenger rna , rna , genetics , gene , endoplasmic reticulum
Induction of p21 in senescent human fibroblasts plays a key role in the inactivation of cyclin‐dependent kinases and the resulting irreversible growth arrest in the early stages of cell senescence. We found that RNA‐binding proteins are critical regulators of p21 during senescence. Two RNA‐binding proteins, CUGBP1 and calreticulin (CRT), interact with the same nucleotide sequences within the 5′ region of p21 mRNA, but have opposite effects on the translation of p21 mRNA. CUGBP1 increases translation of p21 mRNA, whereas CRT blocks translation of p21 via stabilization of a stem–loop structure within the 5′ region of the p21 mRNA. CUGBP1 and CRT compete for binding to p21 mRNA and thereby the regulation of p21 translation. In senescent fibroblasts, CUGBP1 displaces CRT from the p21 mRNA and releases CRT‐dependent repression of p21 translation leading to growth arrest and development of a senescent phenotype. These data present evidence that competition between RNA‐binding proteins for the regulation of p21 translation determines cell fate.