Phosphorylation of PBK/TOPK Tyr74 by JAK2 promotes Burkitt lymphoma tumor growth. (28th September 2022) - Wang, Kaijing
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 . Highlights: TOPK is highly expressed in BL tumor cells. TOPK directly binds to and is phosphorylated at Tyr74 by JAK2, which increases its activity. Phosphorylation of TOPK at Tyr74 by JAK2 promotes carcinogenesis ex vivo. Phosphorylation of TOPK at Tyr74 by JAK2 enhances the stability of TOPK. Phosphorylation of TOPK at Tyr74 by JAK2 promotes BL tumor growth in vivo.