Lamin A precursor induces barrier-to-autointegration factor nuclear localization

Cristina Capanni, Vittoria Cenni, Tokuko Haraguchi, Stefano Squarzoni, Stefan Schüchner, Egon Ogris, Giuseppe Novelli, Nadir Mario Maraldi, Giovanna Lattanzi

Research output: Contribution to journalArticle

Abstract

Lamin A, a protein component of the nuclear lamina, is synthesized as a precursor named prelamin A, whose multi-step maturation process involves different protein intermediates. As demonstrated in laminopathies such as familial partial lipodystrophy, mandibuloacral dysplasia, Werner syndrome, Hutchinson-Gilford progeria syndrome and restrictive dermopathy, failure of prelamin A processing results in the accumulation of lamin A protein precursors inside the nucleus which dominantly produces aberrant chromatin structure. To understand if nuclear lamina components may be involved in prelamin A chromatin remodeling effects, we investigated barrier-to-autointegration factor (BAF) localization and expression in prelamin A accumulating cells. BAF is a DNA-binding protein that interacts directly with histones, lamins and LEM-domain proteins and has roles in chromatin structure, mitosis and gene regulation. In this study, we show that the BAF heterogeneous localization between nucleus and cytoplasm observed in HEK293 cycling cells changes in response to prelamin A accumulation. In particular, we observed that the accumulation of lamin A, non-farnesylated prelamin A and farnesylated carboxymethylated lamin A precursors induce BAF nuclear translocation. Moreover, we show that the treatment of human fibroblasts with prelamin A interfering drugs results in similar changes. Finally, we report that the accumulation of progerin, a truncated form of farnesylated and carboxymethylated prelamin A identified in Hutchinson-Gilford progeria syndrome cells, induces BAF recruitment in the nucleus. These findings are supported by coimmunoprecipitation of prelamin A or progerin with BAF in vivo and suggest that BAF could mediate prelamin A-induced chromatin effects.

Original languageEnglish
Pages (from-to)2600-2610
Number of pages11
JournalCell Cycle
Volume9
Issue number13
DOIs
Publication statusPublished - Jul 1 2010

Keywords

  • BAF
  • HGPS
  • Laminopathies
  • Prelamin A
  • Progerin

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

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  • Cite this

    Capanni, C., Cenni, V., Haraguchi, T., Squarzoni, S., Schüchner, S., Ogris, E., Novelli, G., Maraldi, N. M., & Lattanzi, G. (2010). Lamin A precursor induces barrier-to-autointegration factor nuclear localization. Cell Cycle, 9(13), 2600-2610. https://doi.org/10.4161/cc.9.13.12080