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Functions of the adaptor protein p66Shc in solid tumors
Yanan Sun,Jie Yang,Zhenyi Ma
Front. Biol.. 2015, 10 (6 ): 487-494.
https://doi.org/10.1007/s11515-015-1376-9
p66Shc is a 66 kDa Src homology 2 domain containing (Shc) adaptor protein homolog. Previous studies have demonstrated that p66Shc is a proapoptotic protein involved in the cellular response to oxidative stress and in regulating mammalian lifespan. However, accumulating evidence also indicates its critical role in solid tumor progression. The expression of p66Shc varies in different types of solid tumors, and it can paradoxically promote as well as suppress tumor progression, survival, and metastasis, depending on the cellular context. In this review, we discuss its functions in various solid tumors, the mechanisms by which it mediates the process of anoikis (detachment-induced cell death), and the epigenetic mechanisms that regulate its expression. These studies indicate the potential of p66Shc as a novel prognostic marker and therapeutic target for the prevention of tumor progression and metastasis.
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Selection of effective and highly thermostable Bacillus subtilis lipase A template as an industrial biocatalyst- A modern computational approach
B. Senthilkumar, D. Meshachpaul, Rao Sethumadhavan, R. Rajasekaran
Front. Biol.. 2015, 10 (6 ): 508-519.
https://doi.org/10.1007/s11515-015-1379-6
Biocatalysts are intrinsically reactive and hence their operational stability is of vital significance for any bioprocess. The setback in biocatalyst stability has been tackled from diverse prospects. Inherently, stable biocatalysts are markedly realized and a regular attempt is being made to seek out new organisms that harbor them. Here, we analyzed the industrial biocatalyst lipase A (Native) of Bacillus subtilis and its six thermostable mutants (2M, 3M, 4M, 6M, 9M and 12M) computationally using conformational sampling technique. Consequently, the various structural events deciphering thermostability like root mean square deviation, root mean square fluctuation, radius of gyration and polar surface area showed mutant 12M to be highly stable with statistical validation. Besides, static model analysis involving intra-molecular interactions, secondary structure, solvent accessibility, hydrogen bond pattern, simulated thermal denaturation and desolvation energy also supported 12M comparatively. Of note, the presence of high secondary structural rigidity and hydrogen bonds increased thermostability and functionality of 12M, thus selecting it as a best template for designing thermostable lipases in future. Also, this study has a significant implication toward a better understanding of conformational sampling in enzyme catalysis and enzyme engineering.
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Long-term dermal exposure to diisononyl phthalate exacerbates atopic dermatitis through oxidative stress in an FITC-induced mouse model
Zhuo Wu,Jingquan Li,Ping Ma,Baizhan Li,Yang Xu
Front. Biol.. 2015, 10 (6 ): 537-545.
https://doi.org/10.1007/s11515-015-1382-y
Diisononyl phthalate (DINP), considered to be an environmentally friendly plasticizer, is now widely used. However, the toxic effects of DINP need to be examined, particularly the effects of long-term dermal DINP exposure. Research into the mechanisms underlying these effects is urgently needed. In this study we examined the exacerbation effect of long-term dermal exposure to DINP in fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS) in mice, and sought the potential molecular mechanisms. Forty-nine male Balb/c mice were subjected to a 40-day dermal exposure to saline or one of three concentrations of DINP and then three rounds of sensitization with vehicle or 0.5% FITC. The results of a histopathological examination and measurement of ear swelling as well as immunological and inflammatory biomarkers (total-immunoglobulin (Ig)E and Th cytokines) supported the notion that high doses of DINP may aggravate atopic dermatitis. We also showed that melatonin, an antioxidant, could decrease the levels of oxidative stress and alleviate FITC-induced CHS suggesting that oxidative stress may be one of the molecular mechanisms to explain the exacerbation effect induced by DINP.
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