Alkylating agent methyl methanesulfonate (MMS) induces a wave of global protein hyperacetylation: implications in cancer cell death.
Protein acetylation modification has been implicated in many cellular processes but the direct evidence for the involvement of protein acetylation in signal transduction is very limited. In the present study, we found that an alkylating agent methyl methanesulfonate (MMS) induces a robust and reversible hyperacetylation of both cytoplasmic and nuclear proteins during the early phase of the cellular response to MMS. Notably, the acetylation level upon MMS treatment was strongly correlated with the susceptibility of cancer cells, and the enhancement of MMS-induced acetylation by histone deacetylase (HDAC) inhibitors was shown to increase the cellular susceptibility. These results suggest protein acetylation is important for the cell death signal transduction pathway and indicate that the use of HDAC inhibitors for the treatment of cancer is relevant.
Lee
Min-Young
MY
Department of Biochemistry, College of Medicine, Dong-A University, 3-1, Dongdaeshin-Dong, Seo-Gu, Busan 602-714, South Korea.
Kim
Myoung-Ae
MA
Kim
Hyun-Ju
HJ
Bae
Yoe-Sik
YS
Park
Joo-In
JI
Kwak
Jong-Young
JY
Chung
Jay H
JH
Yun
Jeanho
J
D000107:Acetylation / Q000187:drug effects; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008741:Methyl Methanesulfonate / Q000008:administration & dosage*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*
D018906:Antineoplastic Agents, Alkylating; D009363:Neoplasm Proteins; D008741:Methyl Methanesulfonate