1.JMJD1C forms condensate to facilitate a RUNX1-dependent gene expression program shared by multiple types of AML cells.
Qian CHEN ; Saisai WANG ; Juqing ZHANG ; Min XIE ; Bin LU ; Jie HE ; Zhuoran ZHEN ; Jing LI ; Jiajun ZHU ; Rong LI ; Pilong LI ; Haifeng WANG ; Christopher R VAKOC ; Robert G ROEDER ; Mo CHEN
Protein & Cell 2025;16(5):338-364
JMJD1C (Jumonji Domain Containing 1C), a member of the lysine demethylase 3 (KDM3) family, is universally required for the survival of several types of acute myeloid leukemia (AML) cells with different genetic mutations, representing a therapeutic opportunity with broad application. Yet how JMJD1C regulates the leukemic programs of various AML cells is largely unexplored. Here we show that JMJD1C interacts with the master hematopoietic transcription factor RUNX1, which thereby recruits JMJD1C to the genome to facilitate a RUNX1-driven transcriptional program that supports leukemic cell survival. The underlying mechanism hinges on the long N-terminal disordered region of JMJD1C, which harbors two inseparable abilities: condensate formation and direct interaction with RUNX1. This dual capability of JMJD1C may influence enhancer-promoter contacts crucial for the expression of key leukemic genes regulated by RUNX1. Our findings demonstrate a previously unappreciated role for the non-catalytic function of JMJD1C in transcriptional regulation, underlying a mechanism shared by different types of leukemias.
Core Binding Factor Alpha 2 Subunit/genetics*
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Humans
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Leukemia, Myeloid, Acute/pathology*
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Jumonji Domain-Containing Histone Demethylases/chemistry*
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Gene Expression Regulation, Leukemic
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Oxidoreductases, N-Demethylating/genetics*
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Cell Line, Tumor
2.Understanding the phase separation characteristics of nucleocapsid protein provides a new therapeutic opportunity against SARS-CoV-2.
Dan ZHAO ; Weifan XU ; Xiaofan ZHANG ; Xiaoting WANG ; Yiyue GE ; Enming YUAN ; Yuanpeng XIONG ; Shenyang WU ; Shuya LI ; Nian WU ; Tingzhong TIAN ; Xiaolong FENG ; Hantao SHU ; Peng LANG ; Jingxin LI ; Fengcai ZHU ; Xiaokun SHEN ; Haitao LI ; Pilong LI ; Jianyang ZENG
Protein & Cell 2021;12(9):734-740
3.Induction of dihydroartemisinin on prostate cancer PC-3 apoptosis and its mechanism
Xiaoling GAO ; Ziguo LUO ; Pilong WANG ; Qingchun LI
Chinese Traditional and Herbal Drugs 1994;0(01):-
Objective To study the induction of dihydroartemisinin(DHA) on prostate cancer PC-3 apoptosis and its possible mechansim.Methods MTT was employed for cellular viability measurement,flow cytometry(FCM) and transmission electron microscopy(TEM) for observation of apoptosis,and immunocytochemical staining(SP) for analyzing the expression of Bcl-2 and Bax proteins in PC-3 cells treated with DHA of different concentration.Results DHA Significantly inhibited the proliferation of PC-3 cells,induced their apotosis in a time-concentration dependent manner,and led to mitochondrial swelling,nuclear fragmentations and apoptosis body formation,down-expression of Bcl-2 protein,and over-expression of Bax protein correspondence with DHA concentration.Conclusion DHA could induce the apoptosis in PC-3 cells by up-regulating Bax protein and down-regulating Bcl-2 protein.
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