| Loss of nucleoplasmic LAP2alpha-lamin A complexes causes erythroid and epidermal progenitor hyperproliferation. | |
| | |
MedLine Citation:
|
PMID: 18849980 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Lamina-associated polypeptide (LAP) 2alpha is a chromatin-associated protein that binds A-type lamins. Mutations in both LAP2alpha and A-type lamins are linked to human diseases called laminopathies, but the molecular mechanisms are poorly understood. The A-type lamin-LAP2alpha complex interacts with and regulates retinoblastoma protein (pRb), but the significance of this interaction in vivo is unknown. Here we address the function of the A-type lamin-LAP2alpha complex with the use of LAP2alpha-deficient mice. We show that LAP2alpha loss causes relocalization of nucleoplasmic A-type lamins to the nuclear envelope and impairs pRb function. This causes inefficient cell-cycle arrest in dense fibroblast cultures and hyperproliferation of epidermal and erythroid progenitor cells in vivo, leading to tissue hyperplasia. Our results support a disease-relevant model in which LAP2alpha defines A-type lamin localization in the nucleoplasm, which in turn affects pRb-mediated regulation of progenitor cell proliferation and differentiation in highly regenerative tissues. |
| | |
Authors:
|
Nana Naetar; Barbara Korbei; Serguei Kozlov; Marc A Kerenyi; Daniela Dorner; Rosana Kral; Ivana Gotic; Peter Fuchs; Tatiana V Cohen; Reginald Bittner; Colin L Stewart; Roland Foisner |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-10-12 |
Journal Detail:
|
Title: Nature cell biology Volume: 10 ISSN: 1476-4679 ISO Abbreviation: Nat. Cell Biol. Publication Date: 2008 Nov |
Date Detail:
|
Created Date: 2008-11-03 Completed Date: 2008-12-10 Revised Date: 2011-09-15 |
Medline Journal Info:
|
Nlm Unique ID: 100890575 Medline TA: Nat Cell Biol Country: England |
Other Details:
|
Languages: eng Pagination: 1341-8 Citation Subset: IM |
Affiliation:
|
Max F. Perutz Laboratories, Medical University of Vienna and University of Vienna, Dr. Bohr-Gasse 9, A-1030 Vienna, Austria. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cell Nucleus / metabolism Cell Proliferation* Cytoplasm / metabolism DNA-Binding Proteins / deficiency, genetics, metabolism* Disease Models, Animal Epidermis / cytology Erythroid Precursor Cells / physiology* Lamin Type A / deficiency, genetics, metabolism* Membrane Proteins / deficiency, genetics, metabolism* Mice Mice, Knockout Stem Cells / cytology, physiology* |
| Grant Support | |
ID/Acronym/Agency:
|
P 17871-B09//Austrian Science Fund FWF |
| Chemical | |
Reg. No./Substance:
|
0/DNA-Binding Proteins; 0/Lamin Type A; 0/Membrane Proteins; 0/lamina-associated polypeptide 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Ubiquitylation of the COMPASS component Swd2 links H2B ubiquitylation to H3K4 trimethylation.
Next Document: KIF1Bbeta- and KIF1A-mediated axonal transport of presynaptic regulator Rab3 occurs in a GTP-depende...