| | |  | | | | Record from Web of Science® | | | | | | |
| p38-dependent phosphorylation of the mRNA decay-promoting factor KSRP controls the stability of select myogenic transcripts |
|
|
| Author(s): Briata P, Forcales SV, Ponassi M, Corte G, Chen CY, Karin M, Puri PL, Gherzi R |
| Source: MOLECULAR CELL Volume: 20 Issue: 6 Pages: 891-903 Published: DEC 22 2005 |
| Times Cited: 58 References: 35 |
| Abstract: Transcriptional and posttranscriptional processes regulate expression of genetic networks in response to environmental cues. The extracellular signal-activated p38 MAP kinase (p38) pathway plays a fundamental role in conversion of myoblasts to differentiated myocytes. p38 phosphorylates specific transcription factors and chromatin-associated proteins promoting assembly of the myogenic transcriptome. Here, we demonstrate that p38 alpha and beta isoforms also control muscle-gene expression positranscriptionally, by stabilizing critical myogenic transcripts. KSRP, an important factor for AU-rich element (ARE)-directed mRNA decay, undergoes p38-dependent phosphorylation during muscle differentiation. KSRP phosphorylated by p38 displays compromised binding to ARE-containing transcripts and fails to promote their rapid decay, although it retains the ability to interact with the mRNA degradation machinery. Overexpression of KSRP selectively impairs induction of ARE-containing early myogenic transcripts, without affecting p38-mediated transcriptional responses. Our results uncover an unanticipated role for KSRP in establishing a biochemical link between differentiation-activated p38 signaling and turnover of myogenic mRNAs. |
| Document Type: Article |
| Language: English |
| Reprint Address: Puri, PL (reprint author), Dulbecco Telethon Inst, Gene Express Lab, San Raffaele Biomed Sci Pk,Via Castel Romano,100, I-00128 Rome, Italy |
Addresses:
1. Dulbecco Telethon Inst, Gene Express Lab, I-00128 Rome, Italy
2. Ist Nazl Ric Canc, I-16132 Genoa, Italy
3. Univ Genoa, Sch Med, DOBIG, I-16132 Genoa, Italy
4. Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA
5. Univ Calif San Diego, La Jolla, CA 92093 USA
6. Burnham Inst, La Jolla, CA 92037 USA |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 998NS |
| ISSN: 1097-2765 |
| DOI: 10.1016/j.molcel.2005.10.021 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |