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Loss of nucleoplasmic LAP2 alpha-lamin A complexes causes erythroid and epidermal progenitor hyperproliferation

  1. Author:
    Naetar, N.
    Korbei, B.
    Kozlov, S.
    Kerenyi, M. A.
    Dorner, D.
    Kral, R.
    Gotic, I.
    Fuchs, P.
    Cohen, T. V.
    Bittner, R.
    Stewart, C. L.
    Foisner, R.

  2. Author Address

    Naetar, Nana, Korbei, Barbara, Kerenyi, Marc A.; Dorner, Daniela, Kral, Rosana, Gotic, Ivana, Fuchs, Peter, Foisner, Roland] Med Univ Vienna, Max F Perutz Labs, A-1030 Vienna, Austria. [Naetar, Nana, Korbei, Barbara, Kerenyi, Marc A.; Dorner, Daniela, Kral, Rosana, Gotic, Ivana, Fuchs, Peter, Foisner, Roland] Univ Vienna, A-1030 Vienna, Austria. [Kozlov, Serguei, Cohen, Tatiana V.; Stewart, Colin L.] NCI, Adv BioSci Labs, Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. [Kerenyi, Marc A.] Vienna Bioctr, Inst Mol Pathol, A-1030 Vienna, Austria. [Bittner, Reginald] Med Univ Vienna, Neuromuscular Res Ctr, Ctr Anat & Cell Biol, A-1090 Vienna, Austria.
    1. Year: 2008
  2. Journal: Nature Cell Biology
    1. 10
    2. 11
    3. Pages: 1341-U213
  4. Type of Article: Article
  1. Abstract:

    Lamina-associated polypeptide (LAP) 2 alpha is a chromatin-associated protein that binds A-type lamins(1,2). Mutations in both LAP2 alpha and A-type lamins are linked to human diseases called laminopathies(3), but the molecular mechanisms are poorly understood. The A-type lamin-LAP2a complex interacts with and regulates retinoblastoma protein (pRb)(4,5), but the significance of this interaction in vivo is unknown. Here we address the function of the A-type lamin-LAP2a complex with the use of LAP2 alpha-deficient mice. We show that LAP2a 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(6) in which LAP2a 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.

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External Sources

  1. PMID: 18849980

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