川东北74
转录因子
转录调控
细胞生物学
调节器
巨噬细胞移动抑制因子
乘客5人
生物
染色质
基因表达调控
发起人
基因表达
基因
癌症研究
细胞因子
分子生物学
遗传学
MHC II级
主要组织相容性复合体
作者
Keren David,Gilgi Friedlander,Bianca Pellegrino,Lihi Radomir,Hadas Lewinsky,Lin Leng,Richard Bucala,Shirly Becker-Herman,Idit Shachar
出处
期刊:Cell Reports
[Elsevier]
日期:2022-11-01
卷期号:41 (5): 111572-111572
被引量:6
标识
DOI:10.1016/j.celrep.2022.111572
摘要
CD74 is receptor for the cytokine macrophage migration inhibitory factor (MIF). MIF binding to CD74 induces a signaling cascade resulting in the release of its cytosolic intracellular domain (CD74-ICD) that serves as a transcriptional regulator in chronic lymphocytic leukemia (CLL) cells. In the current study, we investigated the transcriptional and regulatory function of CD74-ICD in normal B cells. We show that following activation, CD74-ICD forms a complex in the cytosol with transcription factors, like PAX5, and binds the chromatin at a significantly higher number of sites compared with its binding in CLL cells. The expression of a major portion of these bound genes is shut down in the malignant cells. The CD74-ICD:PAX5 complex binds the promoter areas of a tumor-suppressor gene, DMTF1, and downregulates its expression through inhibition of transcription. These findings can help identify novel therapeutic pathways that are regulated during oncogenic transformation and are targets for future treatments.
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