In the era of advancement,the entire world continues to remain baffled by the increased rate of progression of cancer.There has been an unending search for novel thera-peutic targets and prognostic markers to curb the...In the era of advancement,the entire world continues to remain baffled by the increased rate of progression of cancer.There has been an unending search for novel thera-peutic targets and prognostic markers to curb the oncogenic scenario.The DEAD-box RNA he-licases are a large family of proteins characterized by their evolutionary conserved D-E-A-D(Asp-Glu-Ala-Asp)domain and merit consideration in the oncogenic platform.They perform multidimensional functions in RNA metabolism and also in the pathology of cancers.Their bio-logical role ranges from ribosome biogenesis,RNA unwinding,splicing,modification of second-ary and tertiary RNA structures to acting as transcriptional coactivators/repressors of various important oncogenic genes.They also play a crucial role in accelerating oncogenesis by pro-moting cell proliferation and metastasis.DDX5(p68)is one of the archetypal members of this family of proteins and has gained a lot of attention due to its oncogenic attribute.It is found to be overexpressed in major cancer types such as colon,brain,breast,and prostate cancer.It exhibits its multifaceted nature by not only coactivating genes implicated in cancers but also mediating crosstalk across major signaling pathways in cancer.Therefore,in this review,we aim to illustrate a comprehensive overview of DEAD-box RNA helicases especially p68 by focusing on their multifaceted roles in different cancers and the various signaling pathways affected by them.Further,we have also briefly discoursed the therapeutic interventional approaches with the DEAD-box RNA helicases as the pharmacological targets for designing in-hibitors to pave way for cancer therapy.展开更多
Foot-and-mouth disease virus(FMDV)can infect domestic and wild cloven-hoofed animals.The non-structural protein 3D plays an important role in FMDV replication and pathogenesis.However,the interaction partners of 3D,an...Foot-and-mouth disease virus(FMDV)can infect domestic and wild cloven-hoofed animals.The non-structural protein 3D plays an important role in FMDV replication and pathogenesis.However,the interaction partners of 3D,and the effects of those interactions on FMDV replication,remain incompletely elucidated.In the present study,using the yeast two-hybrid system,we identified a porcine cell protein,DEAD-box RNA helicase 1(DDX1),which interacted with FMDV 3D.The DDX1-3D interaction was further confirmed by co-immunoprecipitation experiments and an indirect immunofluorescence assay(IFA)in porcine kidney 15(PK-15)cells.DDX1 was reported to either inhibit or facilitate viral replication and regulate host innate immune responses.However,the roles of DDX1 during FMDV infection remain unclear.Our results revealed that DDX1 inhibited FMDV replication in an ATPase/helicase activity-dependent manner.In addition,DDX1 stimulated IFN-p activation in FMDV-infected cells.Together,our results expand the body of knowledge regarding the role of DDX1 in FMDV infection.展开更多
RNA helicases are involved in almost every aspect of RNA, from transcription to RNA decay. DExD/H-box hell- cases compdse the largest SF2 helicase superfamily, which are characterized by two conserved RecA-like domain...RNA helicases are involved in almost every aspect of RNA, from transcription to RNA decay. DExD/H-box hell- cases compdse the largest SF2 helicase superfamily, which are characterized by two conserved RecA-like domains. In recent years, an increasing number of unexpected functions of these proteins have been discovered. They play important roles not only in innate immune response but also in diseases like cancers and chronic hepatitis C. In this review, we summarize the recant literatures on one member of the SF2 superfamily, the DEAD- box protein DDX41. After bacterial or viral infection, DNA or cyclic-di-GMP is released to cells. After phosphorylation of Tyr414 by BTK kinase, DDX41 will act as a sensor to recognize the invaders, followed by induction of type I interferons （IFN）. After the immune response, DDX41 is degraded by the E3 ligase TRIM21, using Lys9 and Lys115 of DDX41 as the ubiquitination sites. Besides the roles in Innate immunity, DDX41 is also related to diseases. An increasing number of both inherited and acquired mutetions in DDX41 gane are identified from myelodysplastic syndrome and/or acute myeloid leukemia （MDS/AML） patients. The review focuses on DDX41, as well as its homolog Abstrakt in Drosophila, which is important for survlval at all stages throughout the life cycle of the fly.展开更多
基金supported by the Department of Science and Technology(Nano Mission:DST/NM/NT/2018/105(G),SERB:EMR/2017/000992/HS&EMR/2017/001183),CSIR(FBR Project#31-2(274)2020-21),Govt.of India.
文摘In the era of advancement,the entire world continues to remain baffled by the increased rate of progression of cancer.There has been an unending search for novel thera-peutic targets and prognostic markers to curb the oncogenic scenario.The DEAD-box RNA he-licases are a large family of proteins characterized by their evolutionary conserved D-E-A-D(Asp-Glu-Ala-Asp)domain and merit consideration in the oncogenic platform.They perform multidimensional functions in RNA metabolism and also in the pathology of cancers.Their bio-logical role ranges from ribosome biogenesis,RNA unwinding,splicing,modification of second-ary and tertiary RNA structures to acting as transcriptional coactivators/repressors of various important oncogenic genes.They also play a crucial role in accelerating oncogenesis by pro-moting cell proliferation and metastasis.DDX5(p68)is one of the archetypal members of this family of proteins and has gained a lot of attention due to its oncogenic attribute.It is found to be overexpressed in major cancer types such as colon,brain,breast,and prostate cancer.It exhibits its multifaceted nature by not only coactivating genes implicated in cancers but also mediating crosstalk across major signaling pathways in cancer.Therefore,in this review,we aim to illustrate a comprehensive overview of DEAD-box RNA helicases especially p68 by focusing on their multifaceted roles in different cancers and the various signaling pathways affected by them.Further,we have also briefly discoursed the therapeutic interventional approaches with the DEAD-box RNA helicases as the pharmacological targets for designing in-hibitors to pave way for cancer therapy.
基金supported by grants from the National Natural Science Foundation of China (Nos. 31302106, 31260616, and 31602035)the National Key Research and Development Program of China (Nos. 2016YFD0500901 and 2017YFD0500903)
文摘Foot-and-mouth disease virus(FMDV)can infect domestic and wild cloven-hoofed animals.The non-structural protein 3D plays an important role in FMDV replication and pathogenesis.However,the interaction partners of 3D,and the effects of those interactions on FMDV replication,remain incompletely elucidated.In the present study,using the yeast two-hybrid system,we identified a porcine cell protein,DEAD-box RNA helicase 1(DDX1),which interacted with FMDV 3D.The DDX1-3D interaction was further confirmed by co-immunoprecipitation experiments and an indirect immunofluorescence assay(IFA)in porcine kidney 15(PK-15)cells.DDX1 was reported to either inhibit or facilitate viral replication and regulate host innate immune responses.However,the roles of DDX1 during FMDV infection remain unclear.Our results revealed that DDX1 inhibited FMDV replication in an ATPase/helicase activity-dependent manner.In addition,DDX1 stimulated IFN-p activation in FMDV-infected cells.Together,our results expand the body of knowledge regarding the role of DDX1 in FMDV infection.
基金ACKNOWLEDGMENTS This work was supported by the National Basic Research Program （973 Program） （No. 2014CB910400 and 2013CB911103）, the National Natural Science Foundation of China （Grants No. 31570875, 31330019, 81590761, 31560727 and 81501353）, the Beijing Nova Program （Grant No. Z141102001814020） to S.O., Youth Innovation Promotion Association CAS （Grant No. 2013065） to S.O., and the special project of Ebola virus research from the president foundation of Chinese Academy of Sciences.
文摘RNA helicases are involved in almost every aspect of RNA, from transcription to RNA decay. DExD/H-box hell- cases compdse the largest SF2 helicase superfamily, which are characterized by two conserved RecA-like domains. In recent years, an increasing number of unexpected functions of these proteins have been discovered. They play important roles not only in innate immune response but also in diseases like cancers and chronic hepatitis C. In this review, we summarize the recant literatures on one member of the SF2 superfamily, the DEAD- box protein DDX41. After bacterial or viral infection, DNA or cyclic-di-GMP is released to cells. After phosphorylation of Tyr414 by BTK kinase, DDX41 will act as a sensor to recognize the invaders, followed by induction of type I interferons （IFN）. After the immune response, DDX41 is degraded by the E3 ligase TRIM21, using Lys9 and Lys115 of DDX41 as the ubiquitination sites. Besides the roles in Innate immunity, DDX41 is also related to diseases. An increasing number of both inherited and acquired mutetions in DDX41 gane are identified from myelodysplastic syndrome and/or acute myeloid leukemia （MDS/AML） patients. The review focuses on DDX41, as well as its homolog Abstrakt in Drosophila, which is important for survlval at all stages throughout the life cycle of the fly.
