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Nucleoplasmic LAP2 alpha-lamin A complexes are required to maintain a proliferative state in human fibroblasts

Pekovic, V; Harborth, J; Broers, JLV; Ramaekers, FCS; van Engelen, B; Lammens, M; von Zglinicki, T; Foisner, R; Hutchison, C; Markiewicz, E

Nucleoplasmic LAP2 alpha-lamin A complexes are required to maintain a proliferative state in human fibroblasts Thumbnail


Authors

V Pekovic

J Harborth

JLV Broers

FCS Ramaekers

B van Engelen

M Lammens

T von Zglinicki

R Foisner

C Hutchison

E Markiewicz



Abstract

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.

Citation

Pekovic, V., Harborth, J., Broers, J., Ramaekers, F., van Engelen, B., Lammens, M., …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), 163-172. https://doi.org/10.1083/jcb.200606139

Journal Article Type Article
Publication Date Jan 1, 2007
Deposit Date Aug 29, 2008
Publicly Available Date Aug 29, 2008
Journal Journal of Cell Biology
Print ISSN 0021-9525
Electronic ISSN 1540-8140
Publisher Rockefeller University Press
Peer Reviewed Peer Reviewed
Volume 176
Issue 2
Pages 163-172
DOI https://doi.org/10.1083/jcb.200606139

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