RT Journal Article
T1 Transcriptional regulation of CDKN2A/p16 by sirtuin 7 in senescence.
A1 Rodriguez, Sergio
A1 Bermudez, Litzy Gisella
A1 Gonzalez, Daniel
A1 Bernal, Camila
A1 Cañas, Alejandra
A1 Morales-Ruiz, Teresa
A1 Henriquez, Berta
A1 Rojas, Adriana
K1 Aging
K1 Cyclin‑dependent kinase inhibitor 2A/p16
K1 Epigenetics
K1 Senescence
K1 Sirtuin 7
AB Cell senescence is a state of limited cell proliferation during a stress response or as part of a programmed process. When a senescent cell stops dividing, maintaining metabolic activity contributes to cellular homeostasis maintenance. In this process, the cell cycle is arrested at the G0/G1 phase. p16INK4A protein is a key regulator of this process via its cyclin‑dependent kinase inhibitor (CDKI) function. CDKI 2A(CDKN2A)/p16 gene expression is regulated by DNA methylation and histone acetylation. Sirtuins (SIRTs) are nicotinamide dinucleotide (NAD+)‑dependent deacetylases that have properties which prevent diseases and reverse certain aspects of aging (such as immune, metabolic and cardiovascular diseases). By performing quantitative PCR, Western blot, ChIP, and siRNAs assays, in this study it was demonstrated that CDKN2A/p16 gene transcriptional activation and repression were accompanied by selective deposition and elimination of histone acetylation during the senescence of MRC5 cells. Specifically, significant H3K9Ac and H3K18Ac enrichment in cells with a senescent phenotype concomitant with CDKN2A/p16 gene overexpression was demonstrated compared with the non‑senescent phenotype. Furthermore, the presence of H3K18Ac in deacetyl‑transferase SIRT7 knockdown MRC5 cells allowed CDKN2A/p16 promoter activation. These results suggested that SIRT7 served as a critical component of an epigenetic mechanism involved in senescence mediated by the CDKN2A/p16 gene.
PB Spandidos Publications
YR 2022
FD 2022-08-17
LK http://hdl.handle.net/10668/21615
UL http://hdl.handle.net/10668/21615
LA en
NO Rodríguez S, Bermúdez LG, González D, Bernal C, Cañas A, Morales-Ruíz T, et al. Transcriptional regulation of CDKN2A/p16 by sirtuin 7 in senescence. Mol Med Rep. 2022 Nov;26(5):345
DS RISalud
RD Apr 12, 2025