Blood:Otub1/c-Maf轴可能是多发性骨髓瘤的潜在治疗靶点

2020-09-03 QQY MedSci原创

致癌转录因子c-Maf已被认为是多发性骨髓瘤(MM)的理想治疗靶点,但如何实现仍不清楚。在该研究中,研究人员发现Otub1/c-Maf轴或可作为潜在的靶点。

致癌转录因子c-Maf已被认为是多发性骨髓瘤(MM)的理想治疗靶点,但如何实现仍不清楚。在该研究中,研究人员发现Otub1/c-Maf轴或可作为潜在的靶点。

Otub1,属于OTU家族去泛素化酶,被发现与c-Maf存在相互作用。Otub1可废除c-Maf K48连接的多聚泛素化,从而防止其降解并增强其转录活性。

具体而言,这种去泛素化活性依赖于其Lys71和N末端,但不依赖UBE2O,一种已知的c-Maf的E2。Otub1促进MM细胞存活和MM肿瘤生长。相反,沉默Otub1可导致c-Maf降解和c-Maf表达性MM细胞凋亡。因此,Otub1/c-Maf轴可能是MM的治疗靶点

为了探索这一推测,研究人员用c-Maf识别原件驱动的荧光素报告试验筛选FDA已批准的药物和自然产物,发现原属强心糖苷,花色苷C (LanC)可通过干扰Otub1和C-Maf的相互作用,阻止C-Maf去泛素化并诱导其降解。进一步实验证明,LanC可抑制c-Maf转录活性,诱导c-Maf表达性MM细胞凋亡、抑制MM生长,并延长小鼠模型的总体存活期,且无明显毒性。

因此,该研究表明,Otub1是c-Maf的一个新的去泛素化酶,提示Otub1/c-Maf可能是MM的潜在治疗靶点。

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    2021-05-26 jml2009
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    2020-09-17 ms4000000956890434

    👌

    0

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    2020-09-03 ms9000000712977569

    写的很好

    0

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