Pekovic, V. and Harborth, J. and Broers, J. L. V. and Ramaekers, F. C. S. and van Engelen, B. and Lammens, M. and von Zglinicki, T. and Foisner, R. and Hutchison, C. and Markiewicz, E. (2007) 'Nucleoplasmic LAP2 alpha-lamin A complexes are required to maintain a proliferative state in human fibroblasts.', Journal of cell biology., 176 (2). pp. 163-172.
In human diploid fibroblasts (HDFs), expression of lamina-associated polypeptide 2 (LAP2) upon entry and exit from G0 is tightly correlated with phosphorylation and subnuclear localization of retinoblastoma protein (Rb). Phosphoisoforms of Rb and LAP2 are down-regulated in G0. Although RbS780 phosphoform and LAP2 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, LAP2 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 LAP2 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 LAP2 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.
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|Publisher Web site:||http://dx.doi.org/10.1083/jcb.200606139|
|Record Created:||29 Aug 2008|
|Last Modified:||08 Sep 2011 09:45|
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