14-3-3ε augments OGT stability by binding with S20-phosphorylated OGT.

The relationship between O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and mitosis is intertwined. Besides the numerous mitotic OGT substrates that have been identified, OGT itself is also a target of the mitotic machinery. Previously, our investigations have shown that Checkpoint kinase 1 (Chk1) phosphorylates OGT at Ser-20 to increase OGT levels during cytokinesis, suggesting that OGT levels oscillate as mitosis progresses. Herein we studied its underlying mechanism. We set out from an R17C mutation of OGT, which is a uterine carcinoma mutation in The Cancer Genome Atlas. We found that R17C abolishes S20 phosphorylation of OGT, as it lies in the Chk1 phosphorylating consensus motif. Consistent with our previous report that pSer-20 is essential for OGT level increases during cytokinesis, we further demonstrate that the R17C mutation renders OGT less stable, decreases vimentin phosphorylation levels and results in cytokinesis defects. Based on bioinformatic predictions, pSer-20 renders OGT more likely to interact with 14-3-3 proteins, the phospho-binding signal adaptor/scaffold protein family. By screening the 7 isoforms of 14-3-3 family, we show that 14-3-3ε specifically associates with Ser-20-phosphorylated OGT. Moreover, we studied the R17C and S20A mutations in xenograft models and demonstrated that they both inhibit uterine carcinoma compared to wild-type OGT, probably due to less cellular reproduction. Our work is a sequel of our previous report on pS20 of OGT and is in line with the notion that OGT is intricately regulated by the mitotic network.

Using scaffolds as drug delivery systems to treat bone tumor.

Surgery is the principal strategy to treat osteosarcoma and other types of bone tumors, but it causes bone defects that cannot be healed spontaneously. After surgery, patients still need to receive radiotherapy and/or chemotherapy to prevent tumor recurrence and metastasis, which leads to systemic side effects. Bone scaffolds exhibit the potentials to load cargos (drugs or growth factors) and act as drug delivery systems (DDSs) in the osteosarcoma postoperative treatment. This review introduces current types of bone scaffolds and highlights representative works using scaffolds as DDSs to treat osteosarcomas. Challenges and perspectives in the scaffold-based DDSs are also discussed. This review may provide references to develop effective and safe strategies for osteosarcoma postoperative treatment.

Catalytic Arylative Endo Cyclization of Gold Acetylides: Access to 3,4-Diphenyl Isoquinoline, 2,3-Diphenyl Indole, and Mesoionic Normal NHC-Gold Complex.

3,4-Diphenyl isoquinoline and 2,3-diphenyl indole are readily accessed by catalytic selective bis-arylative endo cyclization of gold acetylides. The synthetic approach could be also extended to prepare six-membered mesoionic NHC complex, which could further undergo deprotonation/complexation to afford 1,3-N-heterocyclic dicarbene (NHDCs) Au2 and Au/Ag complexes. The key vicinal diaurated alkene intermediates have been isolated and the studies on their reactivities towards coupling partners reinforce the proposed mechanisms.