We recently identified lamin A/C as a docking molecule for human histone deacetylase 2 (HDAC2) and showed involvement of HDAC2-lamin NC complexes in the DNA damage response. We further showed that lamin NC-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 NC 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 NC-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 NC functionality in normal and progeroid cells.
Statins and histone deacetylase inhibitors affect lamin A/C - histone deacetylase 2 interaction in human cells / Mattioli, Elisabetta; Andrenacci, Davide; Mai, Antonello; Valente, Sergio; Robijns, Joke; De Vos, Winnok H; Capanni, Cristina; Lattanzi, Giovanna. - In: FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY. - ISSN 2296-634X. - 7:(2019). [10.3389/fcell.2019.00006]
Statins and histone deacetylase inhibitors affect lamin A/C - histone deacetylase 2 interaction in human cells
Mai, Antonello;Valente, Sergio;
2019
Abstract
We recently identified lamin A/C as a docking molecule for human histone deacetylase 2 (HDAC2) and showed involvement of HDAC2-lamin NC complexes in the DNA damage response. We further showed that lamin NC-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 NC 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 NC-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 NC functionality in normal and progeroid cells.File | Dimensione | Formato | |
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