Menin as a hub controlling mixed lineage leukemia.
Menin as a hub controlling mixed lineage leukemia.
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DOI：
10.1002/bies.201200007
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发表时间：
2012-09
期刊：
影响因子：
4
通讯作者：
Hua, Xianxin
中科院分区：
文献类型：
--
作者：
Thiel, Austin T.;Huang, Jing;Lei, Ming;Hua, Xianxin
Mixed lineage leukemia (MLL) fusion protein (FP)-induced acute leukemia is highly aggressive and often refractory to therapy. Recent progress in the field has unraveled novel mechanisms and targets to combat this disease. Menin, a nuclear protein, interacts with wild-type (WT) MLL, MLL-FPs and other partners such as the chromatin-associated protein LEDGF and the transcription factor c-myb to promote leukemogenesis. The newly solved co-crystal structure illustrating the menin-MLL interaction, coupled with the role of menin in recruiting both WT MLL and MLL-FPs to target genes, highlights menin as a scaffold protein and a central hub controlling this type of leukemia. The menin/WT MLL/MLL-FP hub may also cooperate with several signaling pathways, including Wnt, GSK3, and bromodomain-containing Brd4-related pathways to sustain MLL-FP-induced leukemogenesis, revealing new therapeutic targets to improve the treatment of MLL-FP leukemias.
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