The human adenovirus type 5 early region 1A （E1A） is one of two oncogenes present in the adenovirus genome and functions by interfering with the activities of cellular regulatory proteins. The E1A gene is alternativ...The human adenovirus type 5 early region 1A （E1A） is one of two oncogenes present in the adenovirus genome and functions by interfering with the activities of cellular regulatory proteins. The E1A gene is alternatively spliced to yield five products. Earlier studies have revealed that E1A can regulate the function of thyroid hormone （T3） receptors （TRs）. However, analysis in yeast compared with transfection studies in mammalian cell cultures yields surprisingly different effects. Here, we have examined the effect of E1A on TR function by using the frog oocyte in vivo system, where the effects of E1A can be studied in the context of chromatin. We demonstrate that different isoforms of E1A have distinct effects on TR function. The two longest forms inhibit both the repression by unliganded TR and activation by T3-bound TR. We further show that E1A binds to unliganded TR to displace the endogenous corepressor nuclear receptor corepressor, thus relieving the repression by unliganded TR. On the other hand, in the presence of T3, E1A inhibits gene activation by T3-bound TR indirectly, through a mechanism that requires its binding domain for the general coactivator p300. Taken together, our results thus indicate that E1A affects TR function through distinct mechanisms that are dependent upon the presence or absence of T3.展开更多
The sudden outbreak of the Coronavirus disease(COVID-19)swept across the world in early 2020,triggering the lockdowns of several billion people across many countries,including China,Spain,India,the U.K.,Italy,France,G...The sudden outbreak of the Coronavirus disease(COVID-19)swept across the world in early 2020,triggering the lockdowns of several billion people across many countries,including China,Spain,India,the U.K.,Italy,France,Germany,Brazil,Russia,and the U.S.The transmission of the virus accelerated rapidly with the most confirmed cases in the U.S.,India,Russia,and Brazil.In response to this national and global emergency,the NSF Spatiotemporal Innovation Center brought together a taskforce of international researchers and assembled implementation strategies to rapidly respond to this crisis,for supporting research,saving lives,and protecting the health of global citizens.This perspective paper presents our collective view on the global health emergency and our effort in collecting,analyzing,and sharing relevant data on global policy and government responses,human mobility,environmental impact,socioeconomical impact;in developing research capabilities and mitigation measures with global scientists,promoting collaborative research on outbreak dynamics,and reflecting on the dynamic responses from human societies.展开更多
文摘The human adenovirus type 5 early region 1A （E1A） is one of two oncogenes present in the adenovirus genome and functions by interfering with the activities of cellular regulatory proteins. The E1A gene is alternatively spliced to yield five products. Earlier studies have revealed that E1A can regulate the function of thyroid hormone （T3） receptors （TRs）. However, analysis in yeast compared with transfection studies in mammalian cell cultures yields surprisingly different effects. Here, we have examined the effect of E1A on TR function by using the frog oocyte in vivo system, where the effects of E1A can be studied in the context of chromatin. We demonstrate that different isoforms of E1A have distinct effects on TR function. The two longest forms inhibit both the repression by unliganded TR and activation by T3-bound TR. We further show that E1A binds to unliganded TR to displace the endogenous corepressor nuclear receptor corepressor, thus relieving the repression by unliganded TR. On the other hand, in the presence of T3, E1A inhibits gene activation by T3-bound TR indirectly, through a mechanism that requires its binding domain for the general coactivator p300. Taken together, our results thus indicate that E1A affects TR function through distinct mechanisms that are dependent upon the presence or absence of T3.
基金NSF(1841520,1835507,1832465,2028791 and 2025783)the NSF Spatiotemporal Innovation Center members.
文摘The sudden outbreak of the Coronavirus disease(COVID-19)swept across the world in early 2020,triggering the lockdowns of several billion people across many countries,including China,Spain,India,the U.K.,Italy,France,Germany,Brazil,Russia,and the U.S.The transmission of the virus accelerated rapidly with the most confirmed cases in the U.S.,India,Russia,and Brazil.In response to this national and global emergency,the NSF Spatiotemporal Innovation Center brought together a taskforce of international researchers and assembled implementation strategies to rapidly respond to this crisis,for supporting research,saving lives,and protecting the health of global citizens.This perspective paper presents our collective view on the global health emergency and our effort in collecting,analyzing,and sharing relevant data on global policy and government responses,human mobility,environmental impact,socioeconomical impact;in developing research capabilities and mitigation measures with global scientists,promoting collaborative research on outbreak dynamics,and reflecting on the dynamic responses from human societies.
