Altered modulation of lamin A/C-HDAC2 interaction and p21 expression during oxidative stress response in HGPS
| Autor: | Davide Gentilini, Giovanna Lattanzi, Sergio Valente, Daniel Remondini, Anna Maria Di Blasio, Emanuela Scarano, Elisabetta Mattioli, Antonello Mai, Davide Andrenacci, Katia Scotlandi, Giulia Piaggio, Sabino Prencipe, Cecilia Garofalo, Lucia Cicchilitti |
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| Přispěvatelé: | Mattioli, Elisabetta, Andrenacci, Davide, Garofalo, Cecilia, Prencipe, Sabino, Scotlandi, Katia, Remondini, Daniel, Gentilini, Davide, Di Blasio, Anna Maria, Valente, Sergio, Scarano, Emanuela, Cicchilitti, Lucia, Piaggio, Giulia, Mai, Antonello, Lattanzi, Giovanna |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Premature aging Senescence congenital hereditary and neonatal diseases and abnormalities Aging CDKN1A (p21WAF1/Cip1) Hutchinson-Gilford progeria syndrome (HGPS) aging histone deacetylase 2 (HDAC2) lamin A/C oxidative stress DNA repair Biology 03 medical and health sciences medicine Hutchinson–Gilford progeria syndrome (HGPS) Progeria oxidative stre integumentary system Histone deacetylase 2 Cell Biology medicine.disease Cell biology 030104 developmental biology Histone biology.protein Original Article Histone deacetylase Lamin |
| Zdroj: | Aging Cell |
| Popis: | Defects in stress response are main determinants of cellular senescence and organism aging. In fibroblasts from patients affected by Hutchinson–Gilford progeria, a severe LMNA‐linked syndrome associated with bone resorption, cardiovascular disorders, and premature aging, we found altered modulation of CDKN1A, encoding p21, upon oxidative stress induction, and accumulation of senescence markers during stress recovery. In this context, we unraveled a dynamic interaction of lamin A/C with HDAC2, an histone deacetylase that regulates CDKN1A expression. In control skin fibroblasts, lamin A/C is part of a protein complex including HDAC2 and its histone substrates; protein interaction is reduced at the onset of DNA damage response and recovered after completion of DNA repair. This interplay parallels modulation of p21 expression and global histone acetylation, and it is disrupted by LMNAmutations leading to progeroid phenotypes. In fact, HGPS cells show impaired lamin A/C‐HDAC2 interplay and accumulation of p21 upon stress recovery. Collectively, these results link altered physical interaction between lamin A/C and HDAC2 to cellular and organism aging. The lamin A/C‐HDAC2 complex may be a novel therapeutic target to slow down progression of progeria symptoms. |
| Databáze: | OpenAIRE |
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