期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 7, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2019.00006
关键词
prelamin A; LMNA gene; HDAC2; statins; HDAC inhibitors; trichostatin A (TSA); chromatin
资金
- AIProSaB
- Italian MIUR PRIN 2016 [20152TE5PK, 2015FBNB5Y]
- IOR 5 per mille project 2013
- IOR 5 per mille project 2014
- AIRC 2016 grant [19162]
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.
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