التفاصيل البيبلوغرافية
| العنوان: |
Alterations in Mitosis and Cell Cycle Progression Caused by a Mutant Lamin a Known to Accelerate Human Aging |
| المؤلفون: |
Dechat, Thomas, Shimi, Takeshi, Adam, Stephen A., Rusinol, Antonio E., Andres, Douglas A., Spielmann, H. Peter, Sinensky, Michael S., Goldman, Robert D. |
| المصدر: |
ETSU Faculty Works. |
| بيانات النشر: |
Digital Commons @ East Tennessee State University. |
| المجموعة: |
East Tennessee State University |
| مصطلحات موضوعية: |
cell division, nuclear lamins, nuclear structure, progeria, protein farnesylation, Biomedical Sciences |
| الوصف: |
Mutations in the gene encoding nuclear lamin A (LA) cause the premature aging disease Hutchinson-Gilford Progeria Syndrome. The most common of these mutations results in the expression of a mutant LA, with a 50-aa deletion within its C terminus. In this study, we demonstrate that this deletion leads to a stable farnesylation and carboxymethylation of the mutant LA (LAΔ50/progerin). These modifications cause an abnormal association of LAΔ507 progerin with membranes during mitosis, which delays the onset and progression of cytokinesis. Furthermore, we demonstrate that the targeting of nuclear envelope/lamina components into daughter cell nuclei in early G 1 is impaired in cells expressing LAΔ50/ progerin. The mutant LA also appears to be responsible for defects in the retinoblastoma protein-mediated transition into S-phase, most likely by inhibiting the hyperphosphorylation of retinoblastoma protein by cyclin D1/cdk4. These results provide insights into the mechanisms responsible for premature aging and also shed light on the role of lamins in the normal process of human aging. |
| Original Identifier: |
oai:dc.etsu.edu:etsu-works-19111 |
| نوع الوثيقة: |
Text |
| DOI: |
10.1073/pnas.0700854104 |
| الإتاحة: |
https://dc.etsu.edu/etsu-works/17845Test |
| رقم الانضمام: |
edsndl.ETSU.oai.dc.etsu.edu.etsu.works.19111 |
| قاعدة البيانات: |
Networked Digital Library of Theses & Dissertations |
