Pregnane X receptor(PXR,NR 112)is a prototypical member of the nuclear receptor superfamily.PXR can be activated by both endobiotics and xenobiotics.As a key xenobiotic receptor,the cellular function of PXR is mostly ...Pregnane X receptor(PXR,NR 112)is a prototypical member of the nuclear receptor superfamily.PXR can be activated by both endobiotics and xenobiotics.As a key xenobiotic receptor,the cellular function of PXR is mostly exerted by its binding to the regulatory gene sequences in a liganddependent manner.Classical downstream target genes of PXR participate in xenobiotic responses,such as detoxification,metabolism and inflammation.Emerging evidence also implicates PXR signaling in the processes of apoptosis,cell cycle arrest,proliferation,angiogenesis and oxidative stress,which are closely related to cancer.Here,we discussed,in addition to the characterization of PXR per se,the biological function and regulatory mechanism of PXR signaling in cancer,and its potential for the targeted prevention and therapeutics.展开更多
Emerging evidence suggests that plasma membrane calcium ATPases (PMCAs) play a key role as regulators of calcium-triggered signal transduction pathways via interaction with partner proteins. PMCAs regulate these pathw...Emerging evidence suggests that plasma membrane calcium ATPases (PMCAs) play a key role as regulators of calcium-triggered signal transduction pathways via interaction with partner proteins. PMCAs regulate these pathways by targeting specific proteins to cellular sub-domains where the levels of intracellular freecalcium are kept low by the calcium ejection properties of PMCAs. According to this model, PMCAs have been shown to interact functionally with the calcium-sensitive proteins neuronal nitric oxide synthase, calmodulindependent serine protein kinase, calcineurin and endothelial nitric oxidase synthase. Transgenic animals with altered expression of PMCAs are being used to evaluate the physiological significance of these interactions. To date, PMCA interactions with calcium-dependent partner proteins have been demonstrated to play a crucial role in the pathophysiology of the cardiovascular system via regulation of the nitric oxide and calcineurin/nuclear factor of activated T cells pathways. This new evidence suggests that PMCAs play a more sophisticated role than the mere ejection of calcium from the cells, by acting as modulators of signaling transduction pathways.展开更多
Estrogen-related receptor gamma(ERRg)is one of three members of the ERR family and remains an orphan,as there are no known natural ligands.ERRg is an inducible transcription factor,and its ligandindependent transcript...Estrogen-related receptor gamma(ERRg)is one of three members of the ERR family and remains an orphan,as there are no known natural ligands.ERRg is an inducible transcription factor,and its ligandindependent transcriptional activity is regulated by co-regulator interactions and post-transcriptional modifications.Recent findings from animal models show that ERRg,as a downstream mediator of multiple extracellular signals,plays a key role in coordinating endocrine and metabolic signals,resulting in changes in glucose,alcohol,lipid,and iron metabolism in the liver.Therefore,dysregulation of this receptor contributes to the pathogenesis of metabolic diseases such as hyperglycemia,insulin resistance,and alcoholic liver injury.Interestingly,ERRg is also involved in responses to bacterial infection.These findings establish the importance of ERRg in the endocrine and metabolic control of liver metabolism,and suggest that ERRg may be a promising therapeutic target for metabolic diseases of the liver.展开更多
基金funded by the National Natural Science Foundation of China(81772972 and 81572703)Guangdong Natural Science Foundation(2015A030313449+4 种基金China)Guangdong Science and Technology Project“Public Research and Capacity Building”Special Project Fund(2014A020212285China)Department of Education,Guangdong Government under the Toptier University Development Scheme for Research and Control of Infectious Diseases(2016026,2015060,and 2015089China).
文摘Pregnane X receptor(PXR,NR 112)is a prototypical member of the nuclear receptor superfamily.PXR can be activated by both endobiotics and xenobiotics.As a key xenobiotic receptor,the cellular function of PXR is mostly exerted by its binding to the regulatory gene sequences in a liganddependent manner.Classical downstream target genes of PXR participate in xenobiotic responses,such as detoxification,metabolism and inflammation.Emerging evidence also implicates PXR signaling in the processes of apoptosis,cell cycle arrest,proliferation,angiogenesis and oxidative stress,which are closely related to cancer.Here,we discussed,in addition to the characterization of PXR per se,the biological function and regulatory mechanism of PXR signaling in cancer,and its potential for the targeted prevention and therapeutics.
基金Supported by The Breast Cancer Campaign and the Research Institute in Healthcare Sciences (Armesilla AL)The Wellcome Trust (Emerson M)
文摘Emerging evidence suggests that plasma membrane calcium ATPases (PMCAs) play a key role as regulators of calcium-triggered signal transduction pathways via interaction with partner proteins. PMCAs regulate these pathways by targeting specific proteins to cellular sub-domains where the levels of intracellular freecalcium are kept low by the calcium ejection properties of PMCAs. According to this model, PMCAs have been shown to interact functionally with the calcium-sensitive proteins neuronal nitric oxide synthase, calmodulindependent serine protein kinase, calcineurin and endothelial nitric oxidase synthase. Transgenic animals with altered expression of PMCAs are being used to evaluate the physiological significance of these interactions. To date, PMCA interactions with calcium-dependent partner proteins have been demonstrated to play a crucial role in the pathophysiology of the cardiovascular system via regulation of the nitric oxide and calcineurin/nuclear factor of activated T cells pathways. This new evidence suggests that PMCAs play a more sophisticated role than the mere ejection of calcium from the cells, by acting as modulators of signaling transduction pathways.
基金This work was supported by National Creative Research Initiatives Grant(No.20110018305 to H.-S.Choi and National Research Foundation(NRF)No.2018R1D1A1B07043953 to D.-K.Kim)the NRF funded by the Korean government(Ministry of Science,ICT&Future Planning and Ministry of Education)also carried out with the support of“Cooperative Research Program for Agriculture Science and Technology Development(No.PJ01280701 to D.-K.Kim)”Rural Development Administration,Republic of Korea.
文摘Estrogen-related receptor gamma(ERRg)is one of three members of the ERR family and remains an orphan,as there are no known natural ligands.ERRg is an inducible transcription factor,and its ligandindependent transcriptional activity is regulated by co-regulator interactions and post-transcriptional modifications.Recent findings from animal models show that ERRg,as a downstream mediator of multiple extracellular signals,plays a key role in coordinating endocrine and metabolic signals,resulting in changes in glucose,alcohol,lipid,and iron metabolism in the liver.Therefore,dysregulation of this receptor contributes to the pathogenesis of metabolic diseases such as hyperglycemia,insulin resistance,and alcoholic liver injury.Interestingly,ERRg is also involved in responses to bacterial infection.These findings establish the importance of ERRg in the endocrine and metabolic control of liver metabolism,and suggest that ERRg may be a promising therapeutic target for metabolic diseases of the liver.
