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在多发性骨髓瘤中,ATF4:p52复合体通过p300/CBP招募来激活瘤增强剂,以调节BACH1

Daniel Aron Ang¹, Nathan Harmston², Yinghui Li¹

¹School of Biological Sciences (SBS), Nanyang Technological University (NTU), 60 Nanyang Drive, Singapore, 637551, Singapore.

|April 18, 2025

概括

研究人员发现,ATF4和p52合作激活多发性骨髓瘤 (MM) 中的增强剂,通过调节BACH1.1,推动癌症的进展. 这一发现为MM病原和潜在的治疗点提供了新的见解.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.

背景情况:

多发性骨髓瘤 (MM) 是一种与预后不佳相关的B细胞恶性瘤.
非正规NF-κB (ncNF-κB) 途径的构成性激活,特别是p52,与MM进展有关.
通过p52调节MM中增强剂活性的确切机制尚不清楚.

研究的目的:

研究MM中协调增强剂活性的机制.
在MM相关增强剂中识别与p52合作的转录因子.
阐明p52-调节增强剂在MM病变发生过程中的作用.

主要方法:

来自MM细胞系和患者样本的H3K27acChIP-seq和ATAC-seq数据的分析.
查与p52合作的转录因子.
调查p52和ATF4.4之间的相互作用.
识别下游目标基因和调控元素.

主要成果:

ATF4与p52相互作用,以调节MM相关增强剂的子集.
该ATF4:p52复合体招募像p300和CBP一样的酸乙转移酶 (HATs).
一个特定的ATF4:p52调节目标基因,BACH1,是由一个超级增强器控制的.
BACH1促进细胞循环的进展和增殖,推动MM的瘤发生.

结论:

在MM中异常增强剂激活与ATF4:p52复合体有机联系.
这种复合体通过调节关键目标基因,如BACH1.1,在MM瘤发生过程中发挥着至关重要的作用.
这些发现提供了对MM进展的机制性见解,并建议针对增强剂调节的潜在治疗策略.

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