Wip1 belongs to the protein phosphatase C (PP2C) family, of which expression is up-regulated by a number of external stresses, and serves as a stress modulator in normal physiological conditions. When overexpressed, premature dephosphorylation of stress-mediators by Wip1 results in abrogation of tumor surveillance, thus Wip1 acts as an oncogene. Previously, the functional regulation of Wip1 in cell-cycle progression by counteracting cellular G1 and G2/M checkpoint activity in response to DNA damage was reported. However, other than in stress conditions, the function and regulatory mechanism of Wip1 has not been fully determined. Herein, we demonstrated that protein regulation of Wip1 occurs in a cell cycle-dependent manner, which is directly governed by APC/C(Cdh1) at the end of mitosis. In particular, we also showed evidence that Wip1 phosphatase activity is closely associated with its own protein stability, suggesting that reduced phosphatase activity of Wip1 during mitosis could trigger its degradation. Furthermore, to verify the physiological role of its phosphatase activity during mitosis, we established doxycycline-inducible cell models, including a Wip1 wild type (WT) and phosphatase dead mutant (Wip1 DA). When ectopically expressing Wip1 WT, we observed a delay in the transition from metaphase to anaphase. In conclusion, these studies show that mitotic degradation of Wip1 by APC/C(Cdh1) is important for normal mitotic progression.
Covalently functionalized water-soluble FeCo/ graphitic shell nanocrystals (fÀFeCo/GC NCs) were synthesized via 1,3-dipolar cycloaddition of azomethine ylides generated in situ from sarcosine and glucose. The FeCo core has superparamagnetic properties at room temperature, and the graphitic shell exhibits near-infrared optical absorbance. Acetylation of the hydroxyl groups on the fÀFeCo/GC NCs gives doubly functionalized FeCo/GC (ffÀFeCo/GC) NCs that are soluble only in organic solvents such as ethyl acetate. The fÀFeCo/GC NCs were shown to be excellent T 1 or T 2 MRI contrast agents. Especially, due to the hydrophilic and compact surface functionalization, fÀFeCo/GC NCs exhibit a doubled r 1 relaxivity and half r 2 /r 1 ratio compared to those of the non-covalently PL-PEG-functionalized FeCo/GC NCs. This work shows not only the first synthesis of covalently functionalized highly water-soluble metal NCs coated with a single-layered graphitic shell, but also for the first time the MR enhancing properties of the covalently functionalized magnetic NCs.[a] Dr.
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