Function and mechanism of TRIM22 targeting eIF4E in the process of NB4 cells differentiation

doi:Leukemia; Cell differentiation; Eukaryotic initiation factor4E; Tripartite motif protein 22

Abstract

Abstract: Objective To investigate the function of tripartite motif protein 22 (TRIM22) and the interaction with eukaryotic translation initiation factor4E (eIF4E) in the differentiation of NB4 cells, one kind of acute promyelocytic leukemia cells, which elucidates the mechanism of TRIM22 targeting to regulate eIF4E. Methods The model of NB4 cells inducing differentiation was established in vitro. The expression changes of gene and protein of TRIM22 and eIF4E were detected by using quantitative realtime polymerase chain reaction (qRTPCR) and Western blotting. In addition, the effect on cell function and protein expression level of eIF4E after adopting electroporation technology to depress or overexpress TRIM22 was detected by CCK8 and flow cytometry. Finally, the interaction of TRIM22 and eIF4E was verified by using coimmunoprecipitation (COIP). Results The mRNA relative expression level of TRIM22 was gradually increasing from 1.01±0.15 to 30.98±2.79 (F=280.700, P=0.000), and the protein relative expression level was gradually increasing from 0.22±0.03 to 0.51±0.05 (F=51.430, P=0.000) after the alltransretinoic acid (ATRA) induction for NB4 cell. However, the mRNA relative expression level of eIF4E was gradually decreasing from 1.01±0.09 to 0.47±0.06 (F=20.520, P=0.000), with the same trend, the protein relative expression level was gradually decreasing from 0.97±0.02 to 0.64±0.09 (F=14.700, P=0.001). The expression level of PECD11b in the TRIM22 overexpression group with ATRA detected by flow cytometry ［(78.80±2.00)%］ was higher than that in the transfection group of empty vetor with ATRA ［(58.70±2.70)%］ (t=9.535, P=0.000) and the cotransfection group with ATRA ［(61.60±3.80)%］ (t=8.187, P=0.000). Meanwhile, the protein level of eIF4E changed reversely after overexpressing the gene level of TRIM22 (t=4.985, P=0.007). The COIP experiment was used to verify the interaction of TRIM22 and eIF4E. Conclusion TRIM22 is able to promote the cell differentiation during the process of NB4 cells differentiation. Furthermore, eIF4E is a target of TRIM22 for binding with, which plays an important role in depressing the expression of eIF4E

Key words: , Leukemia, Cell differentiation, Eukaryotic initiation factor-4E, Tripartite motif protein 22

Han Yang, Song Guanhua, Tian Jing, Liao Qiong, Li Lianlian, Zhang Xiaoyu, Liu Hongyan, Zhang Zhiyong, Jiang Guosheng. Function and mechanism of TRIM22 targeting eIF4E in the process of NB4 cells differentiation[J]. Journal of International Oncology, 2017, 44(4): 251-256.

References

［1］ Hattlmann CJ, Kelly JN, Barr SD. TRIM22: a diverse and dynamic antiviral protein［J］. Mol Biol Int, 2012, 2012: 153415. DOI: 10.1155/2012/153415. ［2］ Yap MW, Stoye JP. TRIM proteins and the innate immune response to viruses［J］. Adv Exp Med Biol, 2012, 770: 93104. ［3］ Sun Y, Ho GH, Koong HN, et al. Downregulation of Tripartitemotif containing 22 expression in breast cancer is associated with a lack of p53mediated induction［J］. Biochem Biophys Res Commun, 2013, 441(3): 600606. DOI: 10.1016/j.bbrc.2013.10.110. ［4］ Singh R, Gaiha G, Werner L, et al. Association of TRIM22 with the type 1 interferon response and viral control during primary HIV1 infection［J］. J Virol, 2011, 85(1): 208216. DOI: 10.1128/JVI.0181010. ［5］ Ovsyannikova IG, Haralambieva IH, Vierkant RA, et al. Associations between polymorphisms in the antiviral TRIM genes and measles vaccine immunity［J］. Hum Immunol, 2013, 74(6): 768774. DOI: 10.1016/j.humimm.2013.01.031. ［6］ Topisirovic I, Svitkin YV, Sonenberg N, et al. Cap and capbinding proteins in the control of gene expression［J］. Wiley Interdiscip Rev RNA, 2011, 2(2): 277298. DOI: 10.1002/wrna.52. ［7］ Zong AZ, Liu YH, Zhang Y, et al. Antitumor activity and the mechanism of SIPS: a sulfated polysaccharide with antimetastatic effect［J］. Carbohydr Polym, 2015, 129: 5054. DOI: 10.1016/j.carbpol.2015.04.017. ［8］ Khosravi S, Tam KJ, Ardekani GS, et al. eIF4E is an adverse prognostic marker of melanoma patient survival by increasing melanoma cell invasion［J］. J Invest Dermatol, 2015, 135(5): 13581367. DOI: 10.1038/jid.2014.552. ［9］ Volpon L, Osborne MJ, Zahreddine H, et al. Conformational changes induced in the eukaryotic translation initiation factor eIF4E by a clinically relevant inhibitor, ribavirin triphosphate［J］. Biochem Biophys Res Commun, 2013, 434(3): 614619. DOI: 10.1016/j.bbrc.2013.03.125. ［10］ Carroll M, Borden KL. The oncogene eIF4E: using biochemical insights to target cancer［J］. J Interferon Cytokine Res, 2013, 33(5): 227238. DOI: 10.1089/jir.2012.0142. ［11］ Willimott S, Beck D, Ahearne MJ, et al. Captranslation inhibitor, 4EGI1, restores sensitivity to ABT737 apoptosis through capdependent and independent mechanisms in chronic lymphocytic leukemia［J］. Clin Cancer Res, 2013, 19(12): 32123223. DOI: 10.1158/10780432.CCR122185. ［12］ Kentsis A, Dwyer EC, Perez JM, et al. The RING domains of the promyelocytic leukemia protein PML and the arenaviral protein Z repress translation by directly inhibiting translation initiation factor eIF4E［J］. J Mol Biol, 2001, 312(4): 609623. DOI: 10.1006/jmbi.2001.5003. ［13］ Rajsbaum R, GarciaSastre A, Versteeg GA. TRIMmunity: the roles of the TRIM E3Ubiquitin ligase family in innate antiviral immunity［J］. J Mol Biol, 2014, 426(6): 12651284. DOI: 10.1016/j.jmb.2013.12.005. ［14］ Ndung′u T. TRIM E3 ligases in HIV infection: can these intrinsic immunity factors be harnessed for novel antiviral strategies?［J］. Virulence, 2011, 2(4): 360366. ［15］ KajasteRudnitski A, Marelli SS, Pultrone C, et al. TRIM22 inhibits HIV1 transcription independently of its E3 ubiquitin ligase activity, Tat, and NFkappaBresponsive long terminal repeat elements［J］. J Virol, 2011, 85(10): 51835196. DOI: 10.1128/JVI.0230210.

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