Suberoylanilide Hydroxamic Acid Treatment Reveals Crosstalks among Proteome, Ubiquitylome and Acetylome in Non-Small Cell Lung Cancer A549 Cell Line

Citations Over TimeTop 10% of 2015 papers

Abstract

Suberoylanilide hydroxamic acid (SAHA) is a well-known histone deacetylase (HDAC) inhibitor and has been used as practical therapy for breast cancer and non-small cell lung cancer (NSCLC). It is previously demonstrated that SAHA treatment could extensively change the profile of acetylome and proteome in cancer cells. However, little is known about the impact of SAHA on other protein modifications and the crosstalks among different modifications and proteome, hindering the deep understanding of SAHA-mediated cancer therapy. In this work, by using SILAC technique, antibody-based affinity enrichment and high-resolution LC-MS/MS analysis, we investigated quantitative proteome, acetylome and ubiquitylome as well as crosstalks among the three datasets in A549 cells toward SAHA treatment. In total, 2968 proteins, 1099 acetylation sites and 1012 ubiquitination sites were quantified in response to SAHA treatment, respectively. With the aid of intensive bioinformatics, we revealed that the proteome and ubiquitylome were negatively related upon SAHA treatment. Moreover, the impact of SAHA on acetylome resulted in 258 up-regulated and 99 down-regulated acetylation sites at the threshold of 1.5 folds. Finally, we identified 55 common sites with both acetylation and ubiquitination, among which ubiquitination level in 43 sites (78.2%) was positive related to acetylation level.

Related Papers

• → SAHA Treatment Reveals the Link between Histone Lysine Acetylation and Proteome in Nonsmall Cell Lung Cancer A549 Cells(2013)39 cited
• → The histone deacetylase inhibitor vorinostat induces calreticulin exposure in childhood brain tumour cells in vitro(2010)28 cited
• Antitumor Effects of the Histone Deacetylase Inhibitor Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) in Human Retinoblastoma Cell Lines: Therapeutic Implications(2008)
• Progress in clinical trial of histone deacetylase (HDAC) inhibitors for non-small cell lung cancers*(2014)
• → Vorinostat, a Histone Deacetylase Inhibitor, as a Candidate Therapy to Treat Liver Pathology in a Niemann-Pick type C Disease Mouse Model(2016)