| RNAi of FACE1 protease results in growth inhibition of human cells expressing lamin A: implications for Hutchinson-Gilford progeria syndrome. | |
| | |
MedLine Citation:
|
PMID: 15671064 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
FACE 1 is the endoprotease responsible for cleavage of prelamin A to lamin A. Transfection of HeLa cells with siRNA for human FACE 1 results in a strong phenotype. Protein and mRNA levels for FACE 1 are knocked down and cell division stops abruptly. Two populations of cells are detected. The first form aberrant mitotic spindles, arrest in mitosis and later enter apoptosis. The second show dramatic changes in nuclear morphology with extensive formation of lobulated nuclei and micronuclei. Using antibodies that specifically recognise prelamin A, but not lamin A, we show that prelamin A accumulates at the nuclear lamina in FACE1 silenced cells, whereas in control cells prelamin A is found in many small nuclear dots, but not at the nuclear lamina. In double knockdown experiments with FACE 1 and lamin A siRNAs, the results depend on which protein is knocked down first. FACE1 knockdown 24 hours prior to lamin A knockdown gives results similar to the single FACE1 knockdown. By contrast, lamin A knockdown 24 hours prior to FACE1 knockdown results in none of the changes described above. Silencing of FACE1 in HL60, a cell line that lacks lamin A, also has no effect. The combined results suggest that prelamin A is a poison in cells subjected to FACE 1 knockdown. Finally, we draw attention to similarities in phenotype between FACE1-silenced HeLa cells and fibroblasts from patients with Hutchinson-Gilford progeria syndrome containing prelamin A mutations that prevent cleavage by the FACE1 endoprotease. |
| | |
Authors:
|
Jens Gruber; Tina Lampe; Mary Osborn; Klaus Weber |
Related Documents
:
|
15659094 - Histone deacetylation is required for progression through mitosis in tobacco cells. 15220534 - Analysis of checkpoint responses to histone deacetylase inhibitors. 12969334 - Actin-filled nuclear invaginations indicate degree of cell de-differentiation. 17825564 - Elys/mel-28 chromatin association coordinates nuclear pore complex assembly and replica... 10857224 - Effects of hydrodynamic and interfacial forces on plant cell suspension systems. 3152764 - Tumour necrosis factor. |
Publication Detail:
|
Type: Journal Article Date: 2005-01-25 |
Journal Detail:
|
Title: Journal of cell science Volume: 118 ISSN: 0021-9533 ISO Abbreviation: J. Cell. Sci. Publication Date: 2005 Feb |
Date Detail:
|
Created Date: 2005-02-09 Completed Date: 2005-05-31 Revised Date: 2007-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0052457 Medline TA: J Cell Sci Country: England |
Other Details:
|
Languages: eng Pagination: 689-96 Citation Subset: IM |
Affiliation:
|
Max Planck Institute for Biophysical Chemistry, Department of Biochemistry, Am Fassberg 11, 37077 Göttingen, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Cell Line Cell Nucleus / ultrastructure Cell Proliferation Hela Cells Humans Lamin Type A / metabolism* Lipoproteins / antagonists & inhibitors, genetics, physiology* Membrane Proteins / antagonists & inhibitors, genetics, physiology* Metalloendopeptidases Metalloproteases / antagonists & inhibitors, genetics, physiology* Mitosis Nuclear Proteins / genetics, metabolism* Phenotype Progeria / genetics Protein Precursors / genetics, metabolism* RNA Interference* |
| Chemical | |
Reg. No./Substance:
|
0/Lamin Type A; 0/Lipoproteins; 0/Membrane Proteins; 0/Nuclear Proteins; 0/Protein Precursors; 0/prelamin A; EC 3.4.-/Metalloproteases; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.84/ZMPSTE24 protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Raf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1c.
Next Document: Repeated exposure of human skin fibroblasts to UVB at subcytotoxic level triggers premature senescen...