The mitochondrial serine hydroxymethyltransferase SHMT2, which catalyzes the rate-limiting step in serine catabolism, drives cancer cell proliferation, but how this role is regulated is undefined. Here, we report that the sirtuin SIRT5 desuccinylates SHMT2 to increase its activity and drive serine catabolism in tumor cells. SIRT5 interaction directly mediated desuccinylation of lysine 280 on SHMT2, which was crucial for activating its enzymatic activity. Conversely, hypersuccinylation of SHMT2 at lysine 280 was sufficient to inhibit its enzymatic activity and downregulate tumor cell growth in vitro and in vivo. Notably, SIRT5 inactivation led to SHMT2 enzymatic downregulation and to abrogated cell growth under metabolic stress. Our results reveal that SHMT2 desuccinylation is a pivotal signal in cancer cells to adapt serine metabolic processes for rapid growth, and they highlight SIRT5 as a candidate target for suppressing serine catabolism as a strategy to block tumor growth.Significance: These findings reveal a novel mechanism for controlling cancer cell proliferation by blocking serine catabolism, as a general strategy to impede tumor growth. Cancer Res; 78(2); 372-86.Ó2017 AACR.
Sufficient amounts of fluorographene sheets with different sheet-size and fluorine/carbon ratio were synthesized for preparing of fluorographene/polyimide hybrids in order to explore the effect of fluorographene on the dielectric properties of hybrid materials. It is found that the fluorine/carbon ratio, width of band gap, and sheet-size of fluorographene play the important roles in determining the final dielectric properties of hybrids. The fluorographene with high fluorine/carbon ratio (F/C ≈ 1) presents broaden band gap, enhanced hydrophobicity, good dispersity and thermal stability, etc. Even at a very low filling, only 1 wt %, its polyimide hybrids exhibited drastically reduced dielectric constants as low as 2.1 without sacrificing thermal stability, improved mechanical properties obviously and decreased water absorption by about 120% to 1.0 wt %. This provides a novel route for improving the dielectric properties of materials and a new thought to carry out the application of fluorographene as an advanced material.
Highlights d Quantitative acetylomics reveals hyperacetylated proteins upon nutrition starvation d Multiple cellular stresses result in p300-dependent PHF5A K29 acetylation d PHF5A K29 acetylation enhances KDM3A expression by stabilizing its mRNA d PHF5A acetylation and KDM3A upregulation predict poor prognosis in colon cancer
It is still a challenge to explore the orientation and location of chemical groups in the two-dimensional derivative of graphene. In this study, polarized attenuated total reflectance Fourier transform infrared spectroscopy (polarized ATR-FTIR) was employed to investigate the orientation and location of C-F groups in the corresponding graphene derivative sheets, which facilitates building a relationship between the bonding nature and fine structure. There were two types of C-F bonding, (C-F)I and (C-F)II, in fluorinated graphene sheets. It was found that (C-F)II bonds were linked at the coplanar carbon atoms in the weakly fluorinated region (CxF, x ≥ 2), whereas the (C-F)I bonds cluster at the strongly deformed carbon framework with a F/C ratio of about 1. The thermostability of (C-F)II is lower than that of (C-F)I bonds. This is because the coplanar structure of the weakly fluorinated region tends to transform to the planar aromatic ring with the breaking of the C-F bond as compared with the strong fluorinated nonplanar region.
The effect of solvent on the chemical structure and properties of fluorinated graphene (FG) was particularly investigated in this work. It is found that the reduction of FG and the weakening of strong covalent C-F bonding take place under the action of some dipolar solvents even at room temperature. The rate of the C-F bond rupture reaction is positively influenced by the dipole moment of solvent and fluorine coverage of FG sheets. Meanwhile, defluorination of FG is controllable through the time and temperature of solvent treatment. These solvents function as the nucleophilic catalysts, promoting chemical transformation, which leads to a series of changes in the structure and properties of FG, such as a decline of fluorine concentration of about 40% and the reduction of thermal stability and band gap from 3 to 2 eV. After the treatment with dipolar solvent N-methyl-2-pyrrolidinone, FG maintained a capacity of 255 mA h g(-1) and a power density of 2986 W kg(-1) at a high discharge rate, while the pristine FG could not be discharged at all. This is called the "solvent activation" effect on the electrochemical performance of FG. The finding may draw attention to the effect of various external factors on the chemical structure and properties of FG, which is of great importance for the realization of the FG's potential.
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