CRIF1 interacting with CDK2 regulates bone marrow microenvironment-induced G0/G1 arrest of leukemia cells.
CRIF1 interacting with CDK2 regulates bone marrow microenvironment-induced G0/G1 arrest of leukemia cells.
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CRIF1 与 CDK2 相互作用调节骨髓微环境诱导的白血病细胞 G0/G1 期停滞
DOI：
10.1371/journal.pone.0085328
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Ran Q;Hao P;Xiao Y;Xiang L;Ye X;Deng X;Zhao J;Li Z
目的检测白血病患者外周血细胞CR 6相互作用因子1（CRIF 1）水平，探讨CRIF 1在白血病细胞周期调控中的作用。方法比较健康人、急性髓系白血病（AML）、缺铁性贫血（IDA）和AML完全缓解（AML-CR）患者骨髓（BM）CRIF 1水平。我们还使用慢病毒介导的过表达或siRNA介导的耗竭来操纵Jurkat细胞中的CRIF 1水平。与骨髓基质细胞（BMSC）的共培养用于诱导白血病细胞周期阻滞并模拟BM微环境。结果AML组CRIF 1 mRNA和蛋白表达均明显降低。CRIF 1过表达增加了停滞在G 0/G1期的Jurkat细胞比例，而内源性CRIF 1的缺失减少了细胞周期停滞。CRIF 1的耗尽逆转了白血病细胞中BMSC诱导的细胞周期停滞。免疫共沉淀显示在细胞周期停滞期间Jurkat细胞中CDK 2与CRIF 1特异性结合。免疫荧光染色显示两种蛋白在细胞核和细胞质中均存在共定位。结论CRIF 1可能通过与CDK 2相互作用，发挥细胞周期蛋白依赖性激酶抑制剂的作用，在骨髓微环境诱导的白血病细胞周期阻滞中发挥调控作用。
Background To assess the level of CR6-interacting factor 1 (CRIF1), a cell cycle negative regulator, in patients with leukemia and investigate the role of CRIF1 in regulating leukemia cell cycle. Methods We compared the CRIF1 level in bone marrow (BM) samples from healthy and acute myeloid leukemia (AML), iron deficiency anemia (IDA) and AML-complete remission (AML-CR) subjects. We also manipulated CRIF1 level in the Jurkat cells using lentivirus-mediated overexpression or siRNA-mediated depletion. Co-culture with the BM stromal cells (BMSCs) was used to induce leukemia cell cycle arrest and mimic the BM microenvironment. Results We found significant decreases of CRIF1 mRNA and protein in the AML group. CRIF1 overexpression increased the proportion of Jurkat cells arrested in G0/G1, while depletion of endogenous CRIF1 decreased cell cycle arrest. Depletion of CRIF1 reversed BMSCs induced cell cycle arrest in leukemia cells. Co-immunoprecipitation showed a specific binding of CDK2 to CRIF1 in Jurkat cells during cell cycle arrest. Co-localization of two proteins in both nucleus and cytoplasm was also observed with immunofluorescent staining. Conclusion CRIF1 may play a regulatory role in the BM microenvironment-induced leukemia cell cycle arrest possibly through interacting with CDK2 and acting as a cyclin-dependent kinase inhibitor.
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影响因子：
--
作者：
Suh, Ji Ho;Shong, Minho;Lee, Keesook
通讯作者：
Lee, Keesook
影响因子：
4.8
作者：
Chung, HK;Yi, YW;Shong, MH
通讯作者：
Shong, MH
影响因子：
11.4
作者：
Kwon, Min-chul;Koo, Bon-Kyoung;Kong, Young-Yun
通讯作者：
Kong, Young-Yun
影响因子：
5.1
作者：
Carroll, William L.;Raetz, Elizabeth A.
通讯作者：
Raetz, Elizabeth A.
DOI：
10.1074/jbc.m109.084590
发表时间：
2010-07-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Kang HJ;Hong YB;Kim HJ;Bae I
通讯作者：
Bae I