Phosphorylation of PBK/TOPK Tyr74 by JAK2 promotes Burkitt lymphoma tumor growth.

Abstract

Burkitt lymphoma (BL), which is characterized by high invasiveness, is a subgroup of non-Hodgkin lymphoma. Although BL is regarded as a highly curable disease, especially for children, some patients unfortunately still do not respond adequately. The understanding of the etiology and molecular mechanisms of BL is still limited, and targeted therapies are still lacking. Here, we found that T-LAK cell-derived protein kinase (TOPK) and phosphorylated Janus kinase 2 (p-JAK2) are highly expressed in the tissues of BL patients. We report that TOPK directly binds to and is phosphorylated at Tyr74 by JAK2. Histone H3, one of the downstream targets of TOPK, is also phosphorylated in vivo and in vitro. Furthermore, we report that the phosphorylation of TOPK at Tyr74 by JAK2 plays a vital role in the proliferation of BL cells and promotes BL tumorigenesis in vivo. Phosphorylation of TOPK at Tyr74 by JAK2 enhances the stability of TOPK. Collectively, our results suggest that the JAK2/TOPK/histone H3 axis plays a key role in the proliferation of BL cells and BL tumorigenesis in vivo.

• Authors: Kaijing Wang, Jie Wei, Jing Ma, Qingge Jia, Yixiong Liu, Jia Chai, Junpeng Xu, Tianqi Xu, Danhui Zhao, Yingmei Wang, Qingguo Yan, Shuangping Guo, Xinjian Guo, Feng Zhu, Linni Fan, Mingyang Li, Zhe Wang
• Journal: Cancer letters (Cancer Lett) Vol. 544 Pg. 215812 (09 28 2022) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 35780928 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Histones
• JAK2 protein, human
• Janus Kinase 2
• Mitogen-Activated Protein Kinase Kinases
• PDZ-binding kinase

Topics

• Burkitt Lymphoma (genetics)
• Cell Line, Tumor
• Cell Transformation, Neoplastic
• Child
• Histones (metabolism)
• Humans
• Janus Kinase 2 (genetics, metabolism)
• Mitogen-Activated Protein Kinase Kinases (metabolism)
• Phosphorylation