Lamina-associated polypeptide 2[alpha] regulates cell cycle progression and differentiation via the retinoblastoma-E2F pathway
Lamina-associated polypeptide (LAP) 2[alpha] is a nonmembrane-bound LAP2 isoform that forms complexes with nucleoplasmic A-type lamins. In this study, we show that the overexpression of LAP2[alpha] in fibroblasts reduced proliferation and delayed entry into the cell cycle from a G0 arrest. In contra...
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Veröffentlicht in: | The Journal of cell biology 2006, Vol.173 (1), p.83-93 |
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creator | Dorner, Daniela Vlcek, Sylvia Foeger, Nicole Gajewski, Andreas Makolm, Christian Gotzmann, Josef Hutchison, Christopher J Foisner, Roland |
description | Lamina-associated polypeptide (LAP) 2[alpha] is a nonmembrane-bound LAP2 isoform that forms complexes with nucleoplasmic A-type lamins. In this study, we show that the overexpression of LAP2[alpha] in fibroblasts reduced proliferation and delayed entry into the cell cycle from a G0 arrest. In contrast, stable down-regulation of LAP2[alpha] by RNA interference accelerated proliferation and interfered with cell cycle exit upon serum starvation. The LAP2[alpha]-linked cell cycle phenotype is mediated by the retinoblastoma (Rb) protein because the LAP2[alpha] COOH terminus directly bound Rb, and overexpressed LAP2[alpha] inhibited E2F/Rb-dependent reporter gene activity in G1 phase in an Rb-dependent manner. Furthermore, LAP2[alpha] associated with promoter sequences in endogenous E2F/Rb-dependent target genes in vivo and negatively affected their expression. In addition, the expression of LAP2[alpha] 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[alpha] on cell cycle progression and differentiation may be highly relevant for the cell- and tissue-specific phenotypes observed in laminopathic diseases. |
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In this study, we show that the overexpression of LAP2[alpha] in fibroblasts reduced proliferation and delayed entry into the cell cycle from a G0 arrest. In contrast, stable down-regulation of LAP2[alpha] by RNA interference accelerated proliferation and interfered with cell cycle exit upon serum starvation. The LAP2[alpha]-linked cell cycle phenotype is mediated by the retinoblastoma (Rb) protein because the LAP2[alpha] COOH terminus directly bound Rb, and overexpressed LAP2[alpha] inhibited E2F/Rb-dependent reporter gene activity in G1 phase in an Rb-dependent manner. Furthermore, LAP2[alpha] associated with promoter sequences in endogenous E2F/Rb-dependent target genes in vivo and negatively affected their expression. In addition, the expression of LAP2[alpha] in proliferating preadipocytes caused the accumulation of hypophosphorylated Rb, which is reminiscent of noncycling cells, and initiated partial differentiation into adipocytes. 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In this study, we show that the overexpression of LAP2[alpha] in fibroblasts reduced proliferation and delayed entry into the cell cycle from a G0 arrest. In contrast, stable down-regulation of LAP2[alpha] by RNA interference accelerated proliferation and interfered with cell cycle exit upon serum starvation. The LAP2[alpha]-linked cell cycle phenotype is mediated by the retinoblastoma (Rb) protein because the LAP2[alpha] COOH terminus directly bound Rb, and overexpressed LAP2[alpha] inhibited E2F/Rb-dependent reporter gene activity in G1 phase in an Rb-dependent manner. Furthermore, LAP2[alpha] associated with promoter sequences in endogenous E2F/Rb-dependent target genes in vivo and negatively affected their expression. In addition, the expression of LAP2[alpha] 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[alpha] on cell cycle progression and differentiation may be highly relevant for the cell- and tissue-specific phenotypes observed in laminopathic diseases.</abstract><pub>The Rockefeller University Press</pub></addata></record> |
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title | Lamina-associated polypeptide 2[alpha] regulates cell cycle progression and differentiation via the retinoblastoma-E2F pathway |
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