title: BMI-1026 treatment can induce SAHF formation by activation of Erk1/2.
abstract: BMI-1026 is a synthetic aminopyrimidine compound that targets cyclin dependent kinases (cdks) and was initially designed as a potential anticancer drug. Even though it has been well documented that BMI-1026 is a potent cdk inhibitor, little is known about the cellular effects of this compound. In this study, we examined the effects of BMI-1026 treatment on inducing premature senescence and then evaluated the biochemical features of BMI-1026-induced premature senescence. From these experiments we determined that BMI-1026 treatment produced several biochemical features of premature senescence and also stimulated expression of mitogen activated protein kinase (MAPK) family proteins. BMI-1026 treatment caused nuclear translocation of activated Erk1/2 and the formation of senescence associated heterochromatin foci in 5 days. The heterochromatin foci formation was perturbed by inhibition of Erk1/2 activation.
authors.affiliation: Department of Biochemistry, College of Medicine, Dankook University, Cheonan 330-714, Korea.
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Seo
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Park
authors.forename: Hyung Su
authors.initials: HS
authors.lastname: Choi
authors.forename: So-Yoon
authors.initials: SY
authors.lastname: Hwang
authors.forename: Jeong-Soo
authors.initials: JS
authors.lastname: Park
authors.forename: Yeon-Sun
authors.initials: YS
authors.lastname: Seong
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D051242:Caveolin 1 / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006570:Heterochromatin / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010636:Phenols / Q000009:adverse effects / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D001616:beta-Galactosidase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C480542:BMI 1026; D051242:Caveolin 1; D004791:Enzyme Inhibitors; D006570:Heterochromatin; D010636:Phenols; D011743:Pyrimidines; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D001616:beta-Galactosidase