Abstract:
: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.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Naetar N,Korbei B,Kozlov S,Kerenyi MA,Dorner D,Kral R,Gotic I,Fuchs P,Cohen TV,Bittner R,Stewart CL,Foisner Rdoi
10.1038/ncb1793subject
Has Abstractpub_date
2008-11-01 00:00:00pages
1341-8issue
11eissn
1465-7392issn
1476-4679pii
ncb1793journal_volume
10pub_type
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