- CBL family E3 ubiquitin ligases control JAK2 ubiquitination and stability in hematopoietic stem cells and myeloid malignancies.
CBL family E3 ubiquitin ligases control JAK2 ubiquitination and stability in hematopoietic stem cells and myeloid malignancies.
Genes & development (2017-06-15)
Kaosheng Lv, Jing Jiang, Ryan Donaghy, Christopher R Riling, Ying Cheng, Vemika Chandra, Krasimira Rozenova, Wei An, Bhopal C Mohapatra, Benjamin T Goetz, Vinodh Pillai, Xu Han, Emily A Todd, Grace R Jeschke, Wallace Y Langdon, Suresh Kumar, Elizabeth O Hexner, Hamid Band, Wei Tong
PMID28611190
초록
Janus kinase 2 (JAK2) is a central kinase in hematopoietic stem/progenitor cells (HSPCs), and its uncontrolled activation is a prominent oncogenic driver of hematopoietic neoplasms. However, molecular mechanisms underlying the regulation of JAK2 have remained elusive. Here we report that the Casitas B-cell lymphoma (CBL) family E3 ubiquitin ligases down-regulate JAK2 stability and signaling via the adaptor protein LNK/SH2B3. We demonstrated that depletion of