Regulator of G protein signaling 12(RGS12)belongs to the superfamily of RGS pro-teins defined by a conserved RGS domain that canonically binds and deactivates heterotrimeric G-proteins.As the largest family member,RGS...Regulator of G protein signaling 12(RGS12)belongs to the superfamily of RGS pro-teins defined by a conserved RGS domain that canonically binds and deactivates heterotrimeric G-proteins.As the largest family member,RGS12 is widely expressed in many cells and tissues.In the past few decades,it has been found that RGS12 affects the activity of various cells in the human body,participates in many physiological and pathological processes,and plays an important role in the pathogenesis of many diseases.Here,we set out to comprehensively re-view the role of RGS12 in human diseases and its mechanisms,highlighting the possibility of RGS12 as a therapeutic target for the treatment of human diseases.展开更多
Ubiquitination has important functions in osteoarthritis(OA),yet the mechanism remains unclear.Here,we identify the regulator of G protein signaling 12(RGS12)in macrophages,which promotes the association between ubiqu...Ubiquitination has important functions in osteoarthritis(OA),yet the mechanism remains unclear.Here,we identify the regulator of G protein signaling 12(RGS12)in macrophages,which promotes the association between ubiquitin and IκB during inflammation.We also find that RGS12 promotes the degradation of IκB through enhancing the ubiquitination whereas the process can be inhibited by MG132.Moreover,the increased ubiquitination further inhibits the expression of MTAP,which can indirectly activate the phosphorylation of IκB.Finally,due to the degradation of IκB,the NF-κB translocates into the nucleus and further promotes the gene expression of cytokines such as IL1β,IL6,and TNFαduring inflammation.Importantly,RGS12 deficiency prevents ubiquitination and inflammation in surgically or chemically induced OA.We conclude that the lack of RGS12 in macrophages interferes with the ubiquitination and degradation of IκB,thereby preventing inflammation and cartilage damage.Our results provide evidence for the relevance of RGS12 in promoting inflammation and regulating immune signaling.展开更多
基金supported by the National Natural Science Foundation of China(No.82100889)China Postdoctoral Science Foundation(No.2024M753868)+1 种基金Chongqing Doctor“Through Train”Project(No.CSTB2022BSXM-JCX0022)Chongqing Shapingba District 2024 Techmology lnnovation Project(No.2024114).
文摘Regulator of G protein signaling 12(RGS12)belongs to the superfamily of RGS pro-teins defined by a conserved RGS domain that canonically binds and deactivates heterotrimeric G-proteins.As the largest family member,RGS12 is widely expressed in many cells and tissues.In the past few decades,it has been found that RGS12 affects the activity of various cells in the human body,participates in many physiological and pathological processes,and plays an important role in the pathogenesis of many diseases.Here,we set out to comprehensively re-view the role of RGS12 in human diseases and its mechanisms,highlighting the possibility of RGS12 as a therapeutic target for the treatment of human diseases.
基金supported by grants from the National Institute on Aging(NIA)(No.AG048388)National Institute of Arthritis and Musculoskeletal and Skin Diseases(NIAMS)(No.AR066101)to S Yangsupported by grant from the Penn Center for Musculoskeletal Disorders(PCMD),NIH/NIAMS P30-AR069619.
文摘Ubiquitination has important functions in osteoarthritis(OA),yet the mechanism remains unclear.Here,we identify the regulator of G protein signaling 12(RGS12)in macrophages,which promotes the association between ubiquitin and IκB during inflammation.We also find that RGS12 promotes the degradation of IκB through enhancing the ubiquitination whereas the process can be inhibited by MG132.Moreover,the increased ubiquitination further inhibits the expression of MTAP,which can indirectly activate the phosphorylation of IκB.Finally,due to the degradation of IκB,the NF-κB translocates into the nucleus and further promotes the gene expression of cytokines such as IL1β,IL6,and TNFαduring inflammation.Importantly,RGS12 deficiency prevents ubiquitination and inflammation in surgically or chemically induced OA.We conclude that the lack of RGS12 in macrophages interferes with the ubiquitination and degradation of IκB,thereby preventing inflammation and cartilage damage.Our results provide evidence for the relevance of RGS12 in promoting inflammation and regulating immune signaling.
