دورية أكاديمية
GENETIC AND MOLECULAR ANALYSES OF P53 IN A JAPANESE FAMILY WITH LI-FRAUMENI SYNDROME
| العنوان: | GENETIC AND MOLECULAR ANALYSES OF P53 IN A JAPANESE FAMILY WITH LI-FRAUMENI SYNDROME |
|---|---|
| المؤلفون: | Kodama Koya, Yano Michihiro, Noguchi Atsuko, Uehara Tomoko, Kosaki Kenjiro, Takahashi Tsutomu |
| بيانات النشر: | 秋田医学会 |
| سنة النشر: | 2020 |
| المجموعة: | Akita University Institutional Repository System (AIR) / 秋田大学学術情報リポジトリ |
| مصطلحات موضوعية: | Li-Fraumeni syndrome, P53, Subcellular localization |
| الوصف: | LiFraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome associated with a broad spectrum of early-onset tumors including bone and soft-tissue sarcoma,central nervous system tumors,leukemia,adrenocortical carcinoma,and breast cancer.This syndrome is associated with the P53 gene in 80% of families that fulfill the clinical criteria.Exome sequencing analysis of the P53 gene was performed on a Japanese family with LFS that includes a 2.5-year-old boy with rhabdomyosarcoma, his mother with osteosarcoma and lung cancer at 11 and 37 years old, respectively, and his maternal grandfather with osteosarcoma and gastric cancer at 12 and 42 years old, respectively. A heterozygous germline mutation in the P53 gene, c.997delC or p.R333Vfs*12 P53, causing a frame-shift and premature termination was identified. p53 protein is a transcription factor that binds to DNA as a tetramer. Each P53 monomer comprises a transactivation domain, a proline-rich domain, a central DNA-binding domain, an oligomerization domain, and a C-terminal domain. The truncated protein, p.R333Vfs*12 P53, was transiently expressed in COS-7 cells and studied for subcellular localization and immunoblotting. The results show that the truncated p.R333Vfs*12 P53 protein is appropriately localized into the nucleus. However,immunoblotting analysis suggested that the truncated p.R333Vfs*12 P53 protein would be unstable and degraded into nonfunctional lower molecular proteins. The predicted defects in oligomerization caused by loss of the C-terminus after residue 333, which is located within the tetramerization domain, may account for LFS in this family. Further study is needed to clarify the molecular explanation for oncogenic predisposition in this family. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | Japanese |
| تدمد: | 0386-6106 |
| العلاقة: | https://air.repo.nii.ac.jp/?action=repository_uri&item_id=4741Test; http://hdl.handle.net/10295/00005087Test; 秋田医学 = AKITA JOURNAL OF MEDICINE(AKITA IGAKU), 46(3), 91-98(2020-03-30); AN00009294; 40022245967; https://air.repo.nii.ac.jp/?action=repository_action_common_download&item_id=4741&item_no=1&attribute_id=22&file_no=1Test |
| الإتاحة: | http://hdl.handle.net/10295/00005087Test https://air.repo.nii.ac.jp/?action=repository_uri&item_id=4741Test https://air.repo.nii.ac.jp/?action=repository_action_common_download&item_id=4741&item_no=1&attribute_id=22&file_no=1Test |
| رقم الانضمام: | edsbas.661A887C |
| قاعدة البيانات: | BASE |
| تدمد: | 03866106 |
|---|