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Nucleoplasmic LAP2α-lamin A complexes are required to maintain a proliferative state in human fibroblasts

Lookup NU author(s): Professor Thomas von Zglinicki

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Abstract

In human diploid fibroblasts (HDFs), expression of lamina-associated polypeptide 2 α (LAP2α) upon entry and exit from G0 is tightly correlated with phosphorylation and subnuclear localization of retinoblastoma protein (Rb). Phosphoisoforms of Rb and LAP2á are down-regulated in G0. Although RbS780 phosphoform and LAP2α are up-regulated upon reentry into G1 and colocalize in the nucleoplasm, RbS795 migrates between nucleoplasmic and speckle compartments. In HDFs, which are null for lamins A/C, LAP2α is mislocalized within nuclear aggregates, and this is correlated with cell cycle arrest and accumulation of Rb within speckles. Nuclear retention of nucleoplasmic Rb during G1 phase but not of speckle-associated Rb depends on lamin A/C. siRNA knock down of LAP2á or lamin A/C in HDFs leads to accumulation of Rb in speckles and G1 arrest, probably because of activation of a cell cycle checkpoint. Our results suggest that LAP2α and lamin A/C are involved in controlling Rb localization and phosphorylation, and a lack or mislocalization of either protein leads to cell cycle arrest in HDFs. © The Rockefeller University Press.

Publication metadata

Author(s): Pekovic V, Harborth J, Broers JLV, Ramaekers FCS, Van Engelen B, Lammens M, Von Zglinicki T, Foisner R, Hutchison C, Markiewicz E

Publication type: Article

Publication status: Published

Journal: Journal of Cell Biology

Year: 2007

Volume: 176

Issue: 2

Pages: 163-172

Date deposited: 26/05/2010

ISSN (print): 0021-9525

ISSN (electronic): 1540-8140

Publisher: Rockefeller University Press

URL: http://dx.doi.org/10.1083/jcb.200606139

DOI: 10.1083/jcb.200606139

PubMed id: 17227891

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