ABL1 and Cofilin1 promote T-cell acute lymphoblastic leukemia cell migration

来源 :生物化学与生物物理学报(英文版) | 被引量 : 0次 | 上传用户:chcespring
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
The 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 inhib-ited 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 mecha-nisms 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 spec-trometry 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.
其他文献
Periodontitis is one of the most common chronic inflammations of the oral cavity,which eventually leads to tooth loss.Betulinic acid (BetA) is an organic acid that has anti-inflammatory effects and is derived from fruits and plants,but its effect on the o
In Sterile Insect Technique (SIT) programs,massive numbers of insects are reared,sterilized,and released in the field to impede reproduction of pest populations.The domestication and rearing processes used to produce insects for SIT programs may have sign
Pulmonary hypertension (PH) associated with congenital heart disease is a progressive hemody-namic disease that can lead to increased pulmonary vascular resistance,vascular remodeling,and even right heart failure and death.LF3 is a novel inhibitor of the
Short-chain chlorinated paraffins(SCCPs)have been listed as a new class of persistent organic pol-lutants by the Stockholm Convention.SCCPs exhibit carcinogenic-,endocrine-,and metabolism-disrupting effects.However,the knowledge of the immunomodulatory ef
Exosomes derived from human umbilical cord mesenchymal stem cells(hUCMSC-Ex)play impor-tant roles in immune and inflammation diseases.However,the role of hUCMSC-Ex in atheroscle-rosis has not been elucidated.In this study,the isolated exosomes were identi
Clostridioides difficile infection (CDI) is a common infection of the gastrointestinal tract.Typically,20%-30% of CDI patients experience recurrent C.difficile infection (RCDI).Although the role of Th17 in infectious and inflammatory diseases including CD
Environmental pollution is currently identified as one of the major drivers of rapid decline of insect populations,and this finding has revitalized interest in insect re-sponses to pollution.We tested the hypothesis that the pollution-induced decline of i
Breast cancer is the most prevalent malignancy among women worldwide.Paclitaxel(Taxol)is a widely applied chemotherapeutic agent against breast cancer.Although Taxol therapy has achieved improvements recently,development of chemoresistance of breast cance
Omega-3 polyunsaturated fatty acids(n-3 PUFAs),essential fatty acids for humans and animals,have been reported to play a beneficial role in a variety of inflammatory diseases.In this study,we investigated the inhibitory effects and potential molecular mec
Stroke is the second leading cause of death and long-term disability worldwide,which lacks effective treatment.Perioperative stroke is associated with much higher rates of mortality and disability.The neuroprotective role of dexmedetomidine(Dex),a highly