Document Detail

Loss of nucleoplasmic LAP2alpha-lamin A complexes causes erythroid and epidermal progenitor hyperproliferation.
MedLine Citation:
PMID:  18849980     Owner:  NLM     Status:  MEDLINE    
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.
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    
Max F. Perutz Laboratories, Medical University of Vienna and University of Vienna, Dr. Bohr-Gasse 9, A-1030 Vienna, Austria.
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MeSH Terms
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, Knockout
Stem Cells / cytology,  physiology*
Grant Support
P 17871-B09//Austrian Science Fund FWF
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

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