دورية أكاديمية
Daxx Functions Are p53-Independent In Vivo .
| العنوان: | Daxx Functions Are p53-Independent In Vivo . |
|---|---|
| المؤلفون: | Wasylishen AR; Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas., Estrella JS; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Pant V; Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas., Chau GP; Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas., Lozano G; Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas. gglozano@mdanderson.org. |
| المصدر: | Molecular cancer research : MCR [Mol Cancer Res] 2018 Oct; Vol. 16 (10), pp. 1523-1529. Date of Electronic Publication: 2018 Jun 14. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 101150042 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-3125 (Electronic) Linking ISSN: 15417786 NLM ISO Abbreviation: Mol Cancer Res |
| أسماء مطبوعة: | Original Publication: Philadelphia, PA : American Association for Cancer Research, c2002- |
| مواضيع طبية MeSH: | Carrier Proteins/*genetics , Intracellular Signaling Peptides and Proteins/*genetics , Neuroendocrine Tumors/*genetics , Nuclear Proteins/*genetics , Pancreatic Neoplasms/*genetics , Tumor Suppressor Protein p53/*genetics, Animals ; Apoptosis/genetics ; Co-Repressor Proteins ; Disease Models, Animal ; Histone Chaperones/genetics ; Histones/genetics ; Humans ; Mice ; Mice, Transgenic ; Molecular Chaperones ; Neuroendocrine Tumors/pathology ; Neuroendocrine Tumors/radiotherapy ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/radiotherapy ; Proto-Oncogene Proteins c-mdm2/genetics ; Radiation Tolerance/genetics ; Signal Transduction/radiation effects ; X-linked Nuclear Protein/genetics |
| مستخلص: | Mutations in the death domain-associated protein (DAXX) have been recently identified in a substantial proportion of human pancreatic neuroendocrine tumors (PanNETs). Remarkably, however, little is known about the physiologic role(s) of DAXX despite in vitro studies suggesting potential functions. Most prominently, and supported by tumor sequencing data, DAXX functions in concert with alpha thalassemia/mental retardation X-linked (ATRX) as a histone chaperone complex for the H3.3 variant. Studies have also identified potential roles in apoptosis, transcription, and negative regulation of the p53 tumor suppressor pathway. Herein, a mouse modeling approach was used to specifically address the latter and no significant genetic interaction between Daxx and the p53 pathway was determined. The embryonic lethal phenotype of Daxx loss is not p53-dependent. In addition, Daxx heterozygosity does not sensitize mice to a sublethal dose of ionizing radiation or alter the survival or tumor phenotype of Mdm2 transgenic mice. However, the data support a tumor suppressor role for DAXX as low-dose ionizing radiation produced a higher proportion of carcinomas in Daxx heterozygous mice than wild-type controls. Implications: While DAXX has important in vivo functions, they are independent of an inhibitory role on the p53 tumor suppressor pathway. Mol Cancer Res; 16(10); 1523-9. ©2018 AACR . (©2018 American Association for Cancer Research.) |
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| معلومات مُعتمدة: | R01 CA047296 United States CA NCI NIH HHS; Canada CIHR |
| المشرفين على المادة: | 0 (Carrier Proteins) 0 (Co-Repressor Proteins) 0 (Daxx protein, mouse) 0 (Histone Chaperones) 0 (Histones) 0 (Intracellular Signaling Peptides and Proteins) 0 (Molecular Chaperones) 0 (Nuclear Proteins) 0 (Trp53 protein, mouse) 0 (Tumor Suppressor Protein p53) EC 2.3.2.27 (Mdm2 protein, mouse) EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2) EC 3.6.4.12 (Atrx protein, mouse) EC 3.6.4.12 (X-linked Nuclear Protein) |
| تواريخ الأحداث: | Date Created: 20180616 Date Completed: 20190730 Latest Revision: 20230202 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC6233723 |
| DOI: | 10.1158/1541-7786.MCR-18-0281 |
| PMID: | 29903771 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3125 |
|---|---|
| DOI: | 10.1158/1541-7786.MCR-18-0281 |