CUEDC2, a novel interacting partner of the SOCS1 protein, plays important roles in the leukaemogenesis of acute myeloid leukaemia.

Downregulation of suppressor of cytokine signalling-1 (SOCS1) is one of the vital reasons for JAK1-STAT3 pathway activation in acute myeloid leukaemia (AML). CUE domain-containing 2 (CUEDC2) was a novel interacting partner of SOCS1 and a positive correlation between the expression of CUEDC2 and SOCS1 was confirmed in primary AML cells and AML cell lines without SOCS1 promoter methylation. We aimed to explore roles of CUEDC2 in regulating ubiquitin-mediated degradation of SOCS1 in the leukaemogenesis of AML.

Effects of JAK2 V556F mutation on the JAK2's activity, structural stability and the transformation of Ba/F3 cells.

Although roles of somatic JAK2 mutations in clonally myeloproliferative neoplasms (MPNs) are well established, roles of germline JAK2 mutations in the pathogenesis of MPNs remain unclear. Recently, a novel activating, germline JAK2 F556V mutation was identified and involved in the pathogenesis of MPNs, but, its pathogenesis mechanism was still unknown. In this study, homology models of JAK2 demonstrated that F556 located between two threonine residues which interacted with ATP phosphate groups by hydrogen bonds, Thr555 with the γ-phosphate and Thr557 with the β-phosphate in the active site of JAK2's JH2 domain.

Mutation of the conserved G66 residue in GS region decreased structural stability and activity of arginine kinase.

Arginine kinase (AK) catalyzes the reversible phosphorylation of arginine by ATP, yielding the phosphoarginine. Amino acid residues in the guanidine specificity (GS) region play important roles in the guanidine-recognition. However, little is known about roles of amino acid residue G66 in the GS region in proteins folding, activity and structural stability.

Roles of amino acid residues H66 and D326 in the creatine kinase activity and structural stability.

Creatine kinase (CK) is a key enzyme for cellular energy metabolism, catalyzing the reversible phosphoryl transfer from phosphocreatine to ADP in vertebrates. CK contains a pair of highly conserved amino acids (H66 and D326) which might play an important role in sustaining the compact structure of CK by linking its N- and C- terminal domains; however the mechanism is still unclear. In this study, spectroscopic, structural modeling and protein folding experiments suggested that D326A, H66P and H66P/D326A mutations led to disruption of the hydrogen bond between those two amino acid residues and form the partially unfolded state which made it easier to be inactivated and unfolded under environmental stresses, and more prone to form insoluble aggregates.

Effects of the I682F mutation on JAK2's activity, structure and stability.

Janus kinase 2 (JAK2) plays important roles in the regulation of varieties cellular processes including cell migration, proliferation and apoptosis. JAK2 I682F genetic mutation existed in the 4-8% of B-cell acute lymphoblastic leukemia (B-ALL). However, roles of this mutation in the development of B-ALL are still unknown.