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Activation of CaMKIIγ potentiates T-cell acute lymphoblastic leukemia leukemogenesis via phosphorylating FOXO3a
| Content Provider | Semantic Scholar |
|---|---|
| Author | Jiang, Xudong Wu, Zhaoxing Lu, Xiaoya Zhang, Xichang Yu, Qingfeng Gan, Yichao Wu, Bowen Xu, Ying Zheng, Weiwei Zhang, Lei Ma, A. Jin Gan, Xiaoxian Huang, Silvia Yu, Xiaofang Huang, Wendong Xu, Rong-zhen |
| Copyright Year | 2017 |
| Abstract | Ca2+/calmodulin-dependent protein kinase II γ (CaMKIIγ) can regulate the proliferation and differentiation of myeloid leukemia cells and accelerate chronic myeloid leukemia blast crisis, but the role of CaMKIIγ in T-cell acute lymphoblastic leukemia (T-ALL) leukemogenesis remains poorly understood. We observed that activated (autophosphorylated) CaMKIIγ was invariably present in T-ALL cell lines and in the majority of primary T-ALL samples. Overexpression of CaMKIIγ enhanced the proliferation, colony formation, in vivo tumorigenesis and increased DNA damage of T-ALL leukemia cells. Furthermore, inhibition of CaMKIIγ activity with a pharmacologic inhibitor, gene knock-out, dominant-negative constructs or enhancement of CaMKIIγ activity by overexpression constructs revealed that the activated CaMKIIγ could phosphorylate FOXO3a. In Jurkat cells, the activated CaMKIIγ phosphorylated FOXO3a via directly or indirectly phosphorylating AKT, excluded FOXO3a from the nucleus and inhibited its transcriptional activity. These results indicate that the activated CaMKIIγ may play a key role in T-ALL leukemogenesis, and targeting CaMKIIγ might be a value approach in the treatment of T-ALL. |
| Starting Page | 75050 |
| Ending Page | 75064 |
| Page Count | 15 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&op=download&page=article&path%5B%5D=20504&path%5B%5D=65374 |
| PubMed reference number | 29088844v1 |
| Alternate Webpage(s) | https://doi.org/10.18632/oncotarget.20504 |
| DOI | 10.18632/oncotarget.20504 |
| Journal | Oncotarget |
| Volume Number | 8 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Blast Phase Carcinogenesis Cell Nucleus Exclusion FOXO3A protein, human Knock-out Leukemia, B-Cell Leukemogenesis Myeloid Leukemia Myeloid Leukemia, Chronic Pharmacology Precursor Cell Lymphoblastic Leukemia Lymphoma Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Proto-Oncogene Proteins c-akt T-Lymphocyte Transcription, Genetic cetirizine hydrochloride 10 MG Oral Tablet eIF-2 Kinase lymphoblast |
| Content Type | Text |
| Resource Type | Article |
