Cellular senescence causes profound changes in gene expression profile. In this study, we used a combined 2D-DIGE and nanoLC-ESI-LIT-MS/MS approach to evaluate the proteomic changes occurring both in replicative and stress-induced senescence of human IMR90 cells. Twenty protein spots were identified as shifting their quantitative representation in the same direction (over- or down-represented) in both conditions of senescence, which were associated with 25 sequence entries. Dedicated experiments demonstrated that the decreased representation of a set of these proteins is associated with the down-regulation of the corresponding mRNAs, indicating that the regulation of these genes during the senescence process occurs at a transcriptional level. We also performed functional studies by silencing nine of these genes in young cells, which demonstrated that RNA interference-mediated knockdown of LEPRE1, LIMA1/EPLIN, MAGOHA and MAGOHB induces a premature senescent phenotype in IMR90 cells. Chromatin immunoprecipitation experiments indicated that the reduced expression of these four genes is associated with changes in the histone methylation pattern of their promoters, as proved by the occurrence of increased repressive H3K27me3 along with decreased active H3K4me3 marks, respectively.

Proteomic analysis reveals novel common genes modulated in both replicative and stress-induced senescence / Succoio, Mariangela; Comegna, Marika; D'Ambrosio, Chiara; Scaloni, Andrea; Cimino, Filiberto; Faraonio, Raffaella. - In: JOURNAL OF PROTEOMICS. - ISSN 1874-3919. - 128:(2015), pp. 18-29. [10.1016/j.jprot.2015.07.010]

Proteomic analysis reveals novel common genes modulated in both replicative and stress-induced senescence

SUCCOIO, MARIANGELA;COMEGNA, Marika;d'AMBROSIO, CHIARA;CIMINO, FILIBERTO;FARAONIO, RAFFAELLA
2015

Abstract

Cellular senescence causes profound changes in gene expression profile. In this study, we used a combined 2D-DIGE and nanoLC-ESI-LIT-MS/MS approach to evaluate the proteomic changes occurring both in replicative and stress-induced senescence of human IMR90 cells. Twenty protein spots were identified as shifting their quantitative representation in the same direction (over- or down-represented) in both conditions of senescence, which were associated with 25 sequence entries. Dedicated experiments demonstrated that the decreased representation of a set of these proteins is associated with the down-regulation of the corresponding mRNAs, indicating that the regulation of these genes during the senescence process occurs at a transcriptional level. We also performed functional studies by silencing nine of these genes in young cells, which demonstrated that RNA interference-mediated knockdown of LEPRE1, LIMA1/EPLIN, MAGOHA and MAGOHB induces a premature senescent phenotype in IMR90 cells. Chromatin immunoprecipitation experiments indicated that the reduced expression of these four genes is associated with changes in the histone methylation pattern of their promoters, as proved by the occurrence of increased repressive H3K27me3 along with decreased active H3K4me3 marks, respectively.
2015
Proteomic analysis reveals novel common genes modulated in both replicative and stress-induced senescence / Succoio, Mariangela; Comegna, Marika; D'Ambrosio, Chiara; Scaloni, Andrea; Cimino, Filiberto; Faraonio, Raffaella. - In: JOURNAL OF PROTEOMICS. - ISSN 1874-3919. - 128:(2015), pp. 18-29. [10.1016/j.jprot.2015.07.010]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/636018
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