Reference - Detail
| RRC ID | 12038 |
|---|---|
| Author | Ichwan SJ, Yamada S, Sumrejkanchanakij P, Ibrahim-Auerkari E, Eto K, Ikeda MA. |
| Title | Defect in serine 46 phosphorylation of p53 contributes to acquisition of p53 resistance in oral squamous cell carcinoma cells. |
| Journal | Oncogene |
| Abstract |
To investigate whether dysregulation of p53 phosphorylation confers tumor resistance to p53, we analysed the effects of wild-type p53 on oral squamous cell carcinoma (SCC) cell lines carrying various mutations of p53. Introduction of exogenous p53 neither induced apoptosis nor suppressed colony formation in HSC-3 cells lacking any detectable p53 and HSC-4 cells expressing mutant p53R248Q protein. Consistently, exogenous p53 did not induce proapoptotic p53-target genes in these p53-resistant cells. We found that phosphorylation of exogenous p53 on serine 46 (Ser46) was severely impaired in HSC-3 but not HSC-4 cells. A mutant mimicking Ser46-phosphorylation (p53S46D) enhanced proapoptotic Noxa promoter activity, and overcame the resistance to p53-mediated apoptosis and growth suppression in HSC-3 cells. Conversely, a mutant defective for Ser46-phosphorylation (p53S46A) failed to suppress the growth of p53-sensitive HSC-2 cells. In contrast to HSC-3 cells, p53S46D had no effect on HSC-4 cells, and inhibition of endogenous p53R248Q by siRNA restored p53-mediated apoptosis in HSC-4 cells, indicating a dominant-negative effect of p53R248Q protein on wild-type p53 function. These results demonstrate that the defect in Ser46 phosphorylation accounts for the p53 resistance of HSC-3 cells, and provide evidence for a mechanism underlying the acquisition of p53 resistance in oral SCC. |
| Volume | 25(8) |
| Pages | 1216-24 |
| Published | 2006-2-23 |
| DOI | 10.1038/sj.onc.1209158 |
| PII | 1209158 |
| PMID | 16247456 |
| MeSH | Adenoviridae / genetics Apoptosis Carcinoma, Non-Small-Cell Lung / genetics Carcinoma, Non-Small-Cell Lung / metabolism Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism* Humans Lung Neoplasms / genetics Lung Neoplasms / metabolism Mouth Neoplasms / genetics Mouth Neoplasms / metabolism* Mutation / genetics* Phosphorylation RNA, Small Interfering / pharmacology Serine / metabolism* Tumor Cells, Cultured Tumor Suppressor Protein p53 / metabolism* |
| IF | 7.971 |
| Times Cited | 40 |
| WOS Category | GENETICS & HEREDITY ONCOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| Altmetric score |
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| DNA material | AxCAhp53WT (forward) (RDB02755) |
| Human and Animal Cells | HSC-3(RCB1975) HSC-2(RCB1945) HSC-4(RCB1902) A549(RCB0098) |