Proto-oncogene Akt plays essential roles in cell proliferation and tumorigenesis. Full activation of Akt is regulated by phosphorylation, ubiquitination, and acetylation. Here we report that SUMOylation of Akt is a novel mechanism for its activation. Systematically analyzing the role of lysine residues in Akt activation revealed that K276, which is located in a SUMOylation consensus motif, is essential for Akt activation. Ectopic or endogenous Akt1 could be modified by SUMOylation. RNA interference-mediated silencing of UBC9 reduced Akt SUMOylation, which was promoted by SUMO E3 ligase PIAS1 and reversed by the SUMO-specific protease SENP1. Although multiple sites on Akt could be SUMOylated, K276 was identified as a major SUMO acceptor site. K276R or E278A mutation reduced SUMOylation of Akt but had little effect on its ubiquitination. Strikingly, these mutations also completely abolished Akt kinase activity. In support of these results, we found that expression of PIAS1 and SUMO1 increased Akt activity, whereas expression of SENP1 reduced Akt1 activity. Interestingly, the cancerderived mutant E17K in Akt1 that occurs in various cancers was more efficiently SUMOylated than wild-type Akt. Moreover, SUMOylation loss dramatically reduced Akt1 E17K-mediated cell proliferation, cell migration, and tumorigenesis. Collectively, our findings establish that Akt SUMOylation provides a novel regulatory mechanism for activating Akt function. Cancer Res; 73(18); 5742-53. Ó2013 AACR.

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Two patterns for the multilayer adsorption.

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Solar-driven interfacial evaporation (SIE) is emerging as an energy-efficient technology to alleviate the global water shortages. However, there is a fatal disadvantage in using SIE, that is, the volatile organic compounds (VOCs) widely present in feedwater would concurrently evaporate and transport in distilled water, which threatens the water safety. Photocatalysis is a sustainable technology for pollution control, and after years of development, it has become a mature method. Considering the restriction by the insufficient reaction of the permeating VOCs on the two-dimensional (2D) light-available interface of conventional materials, a 3D photocatalytic approach can be established to boost VOC rejection for photothermal evaporation. In the present work, a light-permeable solar evaporator with 3D photocatalytic sites is constructed by a porous sponge decorated with BiOBrI nanosheets with oxygen-rich vacancies. The 3D microchannels in the evaporator provide a light-permeable path with the deepest irradiation depth of about 580 μm, and the reactive interface is increased by tens of times compared with the traditional 2D membrane, resulting in suppression of VOC remnants in distilled water by around four orders of magnitude. When evaporating river water containing 5 mg L–1 extra added phenol, no phenol residues (below 0.001 mg/L) were detected in the produced freshwater. This development is believed to provide a powerful strategy to resolve the VOC bottleneck of SIE.

The new inorganic/organic hybrid π ligand [Me2C(C5H4)(C2B9H10)]3− was prepared via a selective deboration of Me2C(C5H5)(C2B10H11) with piperidine in ethanol. Treatment of its sodium salt with MCl4(THF)2 gave the mixed-sandwich complexes [{η5:η5-Me2C(C5H4)(C2B9H10)}MCl2][Na(DME)3] (M = Zr (4), Hf (5)). Complex 4 reacted with C5H5Na, KCH2Ph, or NaNH(C6H3-2,6-Pr i 2) to afford {[η5:η2-Me2C(C5H4)(C2B9H10)]Zr(η5-C5H5)(μ-Cl)}{Na(DME)2} (7), [{η5:η5-Me2C(C5H4)(C2B9H10)}ZrCl(CH2C6H5)][Na(DME)3] (8), or [η5:η5-Me2C(C5H4)(C2B9H10)]Zr(NHC6H3Pr i 2)(THF) (9), respectively. Both 7 and 8 were stable, and no NaCl elimination was observed upon heating the toluene solution. In the presence of excess MAO (methylalumoxane), complexes 4, 5, and 8 were very active catalysts for ethylene polymerization. All complexes were fully characterized by various spectroscopic techniques and elemental analyses. Some were further confirmed by single-crystal X-ray analyses.