D Dorner
Lamina-associated polypeptide 2 alpha regulates cell cycle progression and differentiation via the retinoblastoma-E2F pathway
Dorner, D; Vlcek, S; Foeger, N; Gajewski, A; Makolm, C; Gotzmann, J; Hutchison, CJ; Foisner, R
Authors
S Vlcek
N Foeger
A Gajewski
C Makolm
J Gotzmann
CJ Hutchison
R Foisner
Abstract
Lamina-associated polypeptide (LAP) 2 is a nonmembrane-bound LAP2 isoform that forms complexes with nucleoplasmic A-type lamins. In this study, we show that the overexpression of LAP2 in fibroblasts reduced proliferation and delayed entry into the cell cycle from a G0 arrest. In contrast, stable down-regulation of LAP2 by RNA interference accelerated proliferation and interfered with cell cycle exit upon serum starvation. The LAP2-linked cell cycle phenotype is mediated by the retinoblastoma (Rb) protein because the LAP2 COOH terminus directly bound Rb, and overexpressed LAP2 inhibited E2F/Rb-dependent reporter gene activity in G1 phase in an Rb-dependent manner. Furthermore, LAP2 associated with promoter sequences in endogenous E2F/Rb-dependent target genes in vivo and negatively affected their expression. In addition, the expression of LAP2 in proliferating preadipocytes caused the accumulation of hypophosphorylated Rb, which is reminiscent of noncycling cells, and initiated partial differentiation into adipocytes. The effects of LAP2 on cell cycle progression and differentiation may be highly relevant for the cell- and tissue-specific phenotypes observed in laminopathic diseases.
Citation
Dorner, D., Vlcek, S., Foeger, N., Gajewski, A., Makolm, C., Gotzmann, J., …Foisner, R. (2006). Lamina-associated polypeptide 2 alpha regulates cell cycle progression and differentiation via the retinoblastoma-E2F pathway. Journal of Cell Biology, 173(1), 83-93. https://doi.org/10.1083/jcb.200511149
Journal Article Type | Article |
---|---|
Publication Date | Apr 1, 2006 |
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 | 173 |
Issue | 1 |
Pages | 83-93 |
DOI | https://doi.org/10.1083/jcb.200511149 |
Public URL | https://durham-repository.worktribe.com/output/1550823 |
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