BackgroundThe ubiquitin-specific protease 28 (USP28) is an oncogenic deubiquitinase, which plays a critical role in tumorigenesis via antagonizing the ubiquitination and degradation of tumor suppressor protein FBXW7-mediated oncogenic substrates. USP28 controls hypoxia-dependent angiogenesis and metastasis by preventing FBXW7-dependent hypoxia-inducible transcription factor-1α (HIF-1α) degradation during hypoxia. However, it remains unclear how USP28 activation and HIF-1α signaling are coordinated in response to hypoxia.MethodsThe in vitro deubiquitinating activity assay was used to determine the regulation of USP28 by hypoxia. The co-immunoprecipitation and GST Pull-down assays were used to determine the interaction between USP28 and SENP1. The in vivo deSUMOylation assay was performed to determine the regulation of USP28 by SENP1. The luciferase reporter assay was used to determine the transcriptional activity of HIF-1α.ResultsHere, we report that USP28 is a SUMOylated protein in normoxia with moderate deubiquitinating activity towards HIF-1α in vitro, while hypoxia and HIF-1α activate USP28 through SENP1-mediated USP28 deSUMOylation to further accumulate HIF-1α protein in cells. In agreement with this, a SUMOylation mutant USP28 showed enhanced ability to increase HIF-1α level as well as control the transcriptional activity of HIF-1α.ConclusionCollectively, our results reveal a novel SENP1–USP28–HIF-1α positive feedback loop to maximize the concentration of HIF-1a protein and amplify its downstream effects during hypoxia response.
In order to guide the planning of urban microclimate, the influencing variables of the heat island intensity (UII) of tall residential quarter in mountain city in spring and summer is quantitatively analyzed. Through experiments and simulations, 6 variables including wind speed(WS), green ratio(GR), impervious ratio(IR), average surface temperature(AST) , shadow ratio(SR), H / W were chosen and summarized as factors by dimension reduction in factors analysis; further, the dominant variables and factors in different time were confirmed through multiple linear regression analysis of the factors/ variables and UII. Results revealed that in the microclimate tests, it is appropriate to make factor analysis when the cumulative contribution rate of a factor is higher than 50%, and the significant correlated factor of UII is horizontal surface factor (HSF) in three fifths of the testing time in July. The variable analysis revealed that the significance of WS on UII is more in cloudy days than that in sunny days; the significance of SR is higher in summer than that in transition seasons and is most in 15:00, it demonstrates that optimal utilization of the building shadings is an effective way to improve the outdoor thermal environment in residential quarters.
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