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Statins and histone deacetylase inhibitors affect lamin A/C histone deacetylase 2 interaction in human cells

Tijdschriftbijdrage - e-publicatie

We recently identified lamin A/C as a docking molecule for human histone deacetylase 2 (HDAC2) and showed involvement of HDAC2-lamin A/C complexes in the DNA damage response. We further showed that lamin A/C-HDAC2 interaction is altered in Hutchinson-Gilford Progeria syndrome and other progeroid laminopathies. Here, we show that both inhibitors of lamin A maturation and small molecules inhibiting HDAC activity affect lamin A/C interaction with HDAC2. While statins, which inhibit prelamin A processing, reduce protein interaction, HDAC inhibitors strengthen protein binding. Moreover, treatment with HDAC inhibitors restored the enfeebled lamin A/C-HDAC2 interaction observed in HGPS cells. Based on these results, we propose that prelamin A levels as well as HDAC2 activation status might influence the extent of HDAC2 recruitment to the lamin A/C-containing platform and contribute to modulate HDAC2 activity. Our study links prelamin A processing to HDAC2 regulation and provides new insights into the effect of statins and histone deacetylase inhibitors on lamin A/C functionality in normal and progeroid cells.
Tijdschrift: Frontiers in Cell and Developmental Biology
ISSN: 2296-634X
Volume: 7
Jaar van publicatie:2019
Trefwoorden:A1 Journal article
BOF-keylabel:ja
BOF-publication weight:3
CSS-citation score:1
Auteurs:International
Authors from:Higher Education
Toegankelijkheid:Open