摘要
背景:应激诱导磷酸化蛋白(STIP)从线虫到人是高度保守的,具有重要的生物学功能。然而,其在白血病方面的功能有待研究。 方法:临床受试者和细胞模型在本研究中用来探索STIP在淋巴细胞白血病的表达。通过siRNA的转染、免疫、细胞计数、细胞周期分析、实时定量PCR、亚细胞分馏实验、免疫沉淀和免疫印迹对STIP在ARH-77的功能进行研究。 结果:基于此,我们发现STIP在临床淋巴细胞白血病受试者和培养的白血病白细胞比在正常细胞表达更好的活性。B淋巴细胞白血病ARH-77细胞中STIP基因的敲除抑制了S期,更低的细胞增殖率,也抑制了AKT和ERK1/2信号通路。有趣的是,当蛋白磷酸酶被花萼海绵诱癌素抑制时,STIP的敲除没有引起p-ERK1/2的去磷酸化,这表明STIP在调节ERK1/2中依赖于蛋白磷酸酶。通过免疫荧光和免疫沉淀试验发现在那些被花萼海绵诱癌素抑制的蛋白磷酸酶中PP1γ与STIP相互作用。STIP与PP1γ的联合可能降低了PP1γ的磷酸化活性,导致ERK1/2信号的超活化。 结论:总的来说,STIP在淋巴细胞白血病中对ERK1/2信号的表达和活性影响表明STIP在白血病方面可作为潜在的治疗靶点或诊断标记物。
关键词: 应激诱导磷酸化蛋白;淋巴性白血病;细胞外信号调节激酶;蛋白磷酸酶1γ
Current Molecular Medicine
Title:STIP Regulates ERK1/2 Signaling Pathway Involved in Interaction with PP1γ in Lymphoblastic Leukemia
Volume: 16 Issue: 8
Author(s): S. Sun, Y. Wang, H. Chen, L. Fang, Y. Cui, X. Han, D. Wu, H. Li, M. Ye, X. Zhao, J. Liu
Affiliation:
关键词: 应激诱导磷酸化蛋白;淋巴性白血病;细胞外信号调节激酶;蛋白磷酸酶1γ
摘要: Background: Sip1/Tuftelin Interacting Protein (STIP) is highly conserved from Caenorhabditis elegans to Homo sapiens and has essential biological functions. However, its function in leukemia remains unknown.
Methods: Clinic samples and cell model were used in this article to investigate the expression of STIP in lymphoblastic leukemia. The functional research of STIP was performed in ARH-77 by siRNA transfection, immunofluorescence, cell count, cell cycle analysis, qRT-PCR, sub-cellular fractionation assays, immunoprecipitation and western blotting.
Results: Here, we found that STIP is more highly expressed in both clinical lymphoblastic leukemia samples and cultured leukemia cells than in normal samples. Knockdown of STIP in B lymphoblastic leukemia ARH-77 cells leads to S phase arrest, lower cell proliferation rates, and suppressed AKT and ERK1/2 signaling pathways. Interestingly, when protein phosphatase was inhibited by Calyculin A, STIP knockdown did not result in the dephosphorylation of p-ERK1/2, suggesting the dependence of STIP on protein phosphatase in the regulation of ERK1/2. Among those protein phosphatase inhibited by Calyculin A, PP1γ was found to interact with STIP proven by immunofluorescence and immunoprecipitation assays. The binding of STIP with PP1γ may decrease the phosphatase activity of PP1γ, resulting in hyper-activated ERK1/2 signaling.
Conclusion: In summary, the high expression and activation effect on the ERK1/2 signaling of STIP in lymphoblastic leukemia suggest that STIP would be a potential therapy target or diagnosis marker for leukemia.
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Cite this article as:
S. Sun, Y. Wang, H. Chen, L. Fang, Y. Cui, X. Han, D. Wu, H. Li, M. Ye, X. Zhao, J. Liu , STIP Regulates ERK1/2 Signaling Pathway Involved in Interaction with PP1γ in Lymphoblastic Leukemia, Current Molecular Medicine 2016; 16 (8) . https://dx.doi.org/10.2174/1566524016666161018154401
DOI https://dx.doi.org/10.2174/1566524016666161018154401 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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