Gadd45a transcriptional induction elicited by the Aurora kinase inhibitor MK-0457 in Bcr-Abl-expressing cells is driven by Oct-1 transcription factor

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• 作者：Manuela Mancini^a ; ^{mancini_manu@yahoo.com} ; Elisa Leo^b ; Michela Aluigi^a ; Chiara Marcozzi^a ; Enrica Borsi^a ; Enza Barbieri^b ; Maria Alessandra Santucci^a
• 关键词：Chronic myeloid leukemia ; Bcr-Abl ; Gadd45a ; G2/M checkpoint ; Oct-1 transcription factor ; Transcriptional regulation ; Chromatin epigenetic modifications
• 刊名：Leukemia Research
• 出版年：2012
• 期刊代码：186_01452126
• 类别：med
• 出版时间：August, 2012
• 卷：36
• 期：8
• 页码：1028-1034
• 文件大小：720 K

摘要

The advantage of Aurora kinase (AK) inhibitors in chronic myeloid leukemia (CML) therapy mostly arises from 鈥渙ff-target鈥?effects on tyrosine kinase (TK) activity of wild type (wt) or mutated Bcr-Abl proteins which drive the disease resistance to imatinib (IM). We proved that the AK inhibitor MK-0457 induces the growth arrest DNA damage-inducible (Gadd) 45a through recruitment of octamer-binding (Oct)-1 transcription factor at a critical promoter region for gene transcription and covalent modifications of histone H3 (lysine 14 acetylation, lysine 9 de-methylation). Such epigenetic chromatin modifications may depict a general mechanism promoting the re-activation of tumor suppressor genes silenced by Bcr-Abl.