转录因子
基因
染色质
癌变
生物
组蛋白
癌症研究
遗传学
细胞生物学
作者
Akihiko Yokoyama,Michael L. Cleary
出处
期刊:Cancer Cell
[Elsevier]
日期:2008-07-01
卷期号:14 (1): 36-46
被引量:466
标识
DOI:10.1016/j.ccr.2008.05.003
摘要
Menin displays the unique ability to either promote oncogenic function in the hematopoietic lineage or suppress tumorigenesis in the endocrine lineage; however, its molecular mechanism of action has not been defined. We demonstrate here that these discordant functions are unified by menin's ability to serve as a molecular adaptor that physically links the MLL (mixed-lineage leukemia) histone methyltransferase with LEDGF (lens epithelium-derived growth factor), a chromatin-associated protein previously implicated in leukemia, autoimmunity, and HIV-1 pathogenesis. LEDGF is required for both MLL-dependent transcription and leukemic transformation. Conversely, a subset of menin mutations in multiple endocrine neoplasia type 1 patients abrogate interaction with LEDGF while preserving MLL interaction but nevertheless compromise MLL/menin-dependent functions. Thus, LEDGF critically associates with MLL and menin at the nexus of transcriptional pathways that are recurrently targeted in diverse diseases.
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