ABL1 and Cofilin1 promote T-cell acute lymphoblastic leukemia cell migration
Subjectsacute lymphoblastic leukemia
cell signalling pathways
T-cell acute lymphoblastic leukemia (T-ALL)
non-receptor tyrosine kinase
Subject Categories::C130 Cell Biology
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AbstractThe fusion gene of ABL1 is closely related to tumor proliferation, invasion, and migration. It has been reported recently that ABL1 itself is required for T-cell acute lymphoblastic leukemia (T-ALL) cell migration induced by CXCL12. Further experiments revealed that ABL1 inhibitor Nilotinib inhibited leukemia cell migration induced by CXCL12, indicating the possible application of Nilotinib in T-ALL leukemia treatment. However, the interacting proteins of ABL1 and the specific mechanisms of their involvement in this process need further investigation. In the present study, ABL1 interacting proteins were characterized and their roles in the process of leukemia cell migration induced by CXCL12 were investigated. Co-immunoprecipitation in combination with mass spectrometry analysis identified 333 proteins that interact with ABL1, including Cofilin1. Gene ontology analysis revealed that many of them were enriched in the intracellular organelle or cytoplasm, including nucleic acid binding components, transfectors, or co-transfectors. Kyoto Encyclopedia of Genes and Genomes analysis showed that the top three enriched pathways were translation, glycan biosynthesis, and metabolism, together with human diseases. ABL1 and Cofilin1 were in the same complex. Cofilin1 binds the SH3 domain of ABL1 directly; however, ABL1 is not required for the phosphorylation of Cofilin1. Molecular docking analysis shows that ABL1 interacts with Cofilin1 mainly through hydrogen bonds and ionic interaction between amino acid residues. The mobility of leukemic cells was significantly decreased by Cofilin1 siRNA. These results demonstrate that Cofilin1 is a novel ABL1 binding partner. Furthermore, Cofilin1 participates in the migration of leukemia cells induced by CXCL12. These data indicate that ABL1 and Cofilin1 are possible targets for T-ALL treatment.
CitationLuo J, Zheng H, Wang S, Li D, Ma W, Wang L, Crabbe MJC (2021) 'ABL1 and Cofilin1 promote T-cell acute lymphoblastic leukemia cell migration', Acta Biochimica et Biophysica Sinica, 53 (10), pp.1321-1332.
PublisherOxford University Press
SponsorsThis work was supported by the grants from the National Natural Science Foundation of China (No. 31401216) and Natural Science Foundation of Shanxi Province of China (No. 201901D111010).
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