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Rad is a p53 direct transcriptional target that inhibits cell migration and is frequently silenced in lung carcinoma cells.
- Source :
-
Journal of Molecular Medicine . May2011, Vol. 89 Issue 5, p481-492. 12p. 4 Diagrams, 1 Chart, 2 Graphs. - Publication Year :
- 2011
-
Abstract
- The p53 tumor suppressor exerts its function mainly as a transcriptional activator. Here we show that the Ras-related small GTPase Rad, an inhibitor of Rho kinase, is a direct transcriptional target of p53. Expression of Rad messenger RNA (mRNA) and protein was induced by DNA damage in a p53-dependent manner. The −2934/−2905-bp Rad promoter region, to which p53 bound, was required for p53-mediated Rad gene activation. Treatment by DNA damaging agents increased p53 occupancy and histone acetylation in the region of Rad promoter containing the p53-binding site. Expression of Rad diminished the inhibitory phosphorylation at Ser3 of cofilin, a regulator of actin dynamics, and suppressed migration and invasiveness of cancer cells. Knockdown of Rad promoted cell migration and alleviated the p53-mediated migration suppression. Frequent loss of Rad mRNA and protein expression was observed in non-small cell lung carcinoma tissues. Together our results reveal a mechanism that p53 may inhibit cell migration by disrupting actin dynamics via Rad activation and implicate a tumor suppressor role of Rad in lung cancer. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CELL migration
*CANCER cells
*LUNG cancer
*MESSENGER RNA
*DNA damage
*ACTIN
Subjects
Details
- Language :
- English
- ISSN :
- 09462716
- Volume :
- 89
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Journal of Molecular Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 60018163
- Full Text :
- https://doi.org/10.1007/s00109-010-0717-z