Phosphorylation of PBK/TOPK Tyr74 by JAK2 promotes Burkitt lymphoma tumor growth.
Burkitt lymphoma
JAK2
Phosphorylation
TOPK
Tumor growth
Journal
Cancer letters
ISSN: 1872-7980
Titre abrégé: Cancer Lett
Pays: Ireland
ID NLM: 7600053
Informations de publication
Date de publication:
28 09 2022
28 09 2022
Historique:
received:
28
03
2022
revised:
08
06
2022
accepted:
27
06
2022
pubmed:
6
7
2022
medline:
10
8
2022
entrez:
5
7
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35780928
pii: S0304-3835(22)00296-8
doi: 10.1016/j.canlet.2022.215812
pii:
doi:
Substances chimiques
Histones
0
JAK2 protein, human
EC 2.7.10.2
Janus Kinase 2
EC 2.7.10.2
Mitogen-Activated Protein Kinase Kinases
EC 2.7.12.2
PDZ-binding kinase
EC 2.7.12.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
215812Informations de copyright
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