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Title
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Statins and histone deacetylase inhibitors affect lamin A/C histone deacetylase 2 interaction in human cells
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Frontiers in Cell and Developmental Biology
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Publication
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2019
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ISSN
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2296-634X
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DOI
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10.3389/FCELL.2019.00006
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Volume/pages
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7
(2019)
, 10 p.
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Article Reference
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UNSP 6
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ISI
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000467197300001
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Pubmed ID
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30766871
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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