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多omics集成通过PBRM1-PIAS1合作识别了细胞状态特定的镇压

Patric J Ho¹, Junghun Kweon¹, Laura A Blumensaadt¹

¹Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.

|January 8, 2024

概括

多囊和肝病1 (PBRM1) 蛋白调节上皮细胞分化. 它的功能根据细胞状态而变化,通过与PIAS1.1的相互作用影响原生细胞的维持和分化.

科学领域:

细胞生物学细胞生物学
分子生物学分子生物学
癌症研究癌症研究

背景情况:

在癌症发病前正常上皮质平衡中,PBRM1的基因调节功能尚不清楚.
在上皮癌中,PBRM1经常发生突变,这表明它在这些组织中起着关键作用.

研究的目的:

为了研究PBRM1在人类皮肤上皮的细胞状态特异性基因调节作用.
阐明PBRM1在维持表皮原生种群和调节分化方面的功能背后的分子机制.

主要方法:

利用人类皮肤上皮作为研究PBRM1.1的模型系统.
进行了针对性的选,以识别PBRM1相互作用蛋白.
研究了SUMOylation在PBRM1功能中的作用.

主要成果:

PBRM1在原始细胞和分化的上皮细胞中表现出不同的基因调节功能.
在原始细胞中,PBRM1抑制分化;在分化的细胞中,它充当激活剂.
PIAS1被确定为一个关键的相互作用蛋白,与PBRM1共同定位,抑制祖先的分化基因.
在分化过程中,PIAS1染色体结合显著下降.
PBRM1的SUMOylation有助于其在祖先维护中的抑制作用.

结论:

PBRM1的基因调节活性取决于细胞状态,在抑制剂和激活剂之间切换.
蛋白互动组,特别是PIAS1,会影响PBRM1的功能.
尽管稳定染色体结合,但PBRM1在表皮平衡中的作用是通过其相互作用和SUMOylation等翻译后修饰来调节的.

关键词:

在BAF中,BAF是BAF.这就是PBRM1的原因.在 PIAS1 的基础上.这就是所谓的SUMO.在 SWI/SNF 中.不同化的差异化差异化.皮肤表皮的表皮.皮质上皮质上皮质上皮质.角质细胞 (keratinocytes) 是一种细胞.原始人的祖先.镇压镇压镇压镇压皮肤皮肤皮肤

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