The innate immune response provides the initial defense against infection. This is accomplished by families of pattern recognition receptors (PRRs) that bind to conserved molecules in bacteria, fungi and viruses. PRRs...The innate immune response provides the initial defense against infection. This is accomplished by families of pattern recognition receptors (PRRs) that bind to conserved molecules in bacteria, fungi and viruses. PRRs are finely regulated by elaborate mechanisms to ensure a beneficial outcome in response to foreign invaders. MicroRNAs (miRNAs) are a class of small non-coding regulatory RNAs that are emerging as important regulators in immune responses at the post-transcriptional level, through the inhibition of translation, or by inducing mRNA degradation. It has been shown that miRNAs have unique expression profiles in cells of the innate immune systems and play pivotal roles in regulating the signal pathways of innate receptors, including Toll-like receptors, RIG-I-like receptors and Nod-like receptors. We have summarized the recent literature providing new insights into the regulation of innate receptor pathways by miRNAs.展开更多
Nuclear distribution gene C (NudC) was first found in Aspergillus nidulans as an upstream regulator of NudF, whose mamma- lian homolog is Lissencephaly 1 (Lisl). NudC is conserved from fungi to mammals. Vertebrate...Nuclear distribution gene C (NudC) was first found in Aspergillus nidulans as an upstream regulator of NudF, whose mamma- lian homolog is Lissencephaly 1 (Lisl). NudC is conserved from fungi to mammals. Vertebrate NudC has three homologs: NudC, NudC-like protein (NudCL), and NudC-like protein 2 (NudCL2). All members of the NudC family share a conserved p23 domain, which possesses chaperone activity both in conjunction with and independently of heat shock protein 90 (Hsp90). Our group and the others found that NudC homologs were involved in cell cycle regulation by stabilizing the components of the LIS l/dynein complex. Additionally, NudC plays important roles in cell migration, ciliogenesis, thrombopoiesis, and the in- flammatory response. It has been reported that NudCL is essential for the stability of the dynein intermediate chain and cilio- genesis via its interaction with the dynein 2 complex. Our data showed that NudCL2 regulates the LISl/dynein pathway by stabilizing LIS 1 with Hsp90 chaperone. The fourth distantly related member of the NudC family, CML66, a tumor-associated antigen in human leukemia, contains a p23 domain and appears to promote oncogenesis by regulating the IGF-1R-MAPK sig- naling pathway. In this review, we summarize our current knowledge of the NudC family and highlight its potential clinical relevance.展开更多
文摘The innate immune response provides the initial defense against infection. This is accomplished by families of pattern recognition receptors (PRRs) that bind to conserved molecules in bacteria, fungi and viruses. PRRs are finely regulated by elaborate mechanisms to ensure a beneficial outcome in response to foreign invaders. MicroRNAs (miRNAs) are a class of small non-coding regulatory RNAs that are emerging as important regulators in immune responses at the post-transcriptional level, through the inhibition of translation, or by inducing mRNA degradation. It has been shown that miRNAs have unique expression profiles in cells of the innate immune systems and play pivotal roles in regulating the signal pathways of innate receptors, including Toll-like receptors, RIG-I-like receptors and Nod-like receptors. We have summarized the recent literature providing new insights into the regulation of innate receptor pathways by miRNAs.
基金supported by the Ministry of Science and Technology of China (2012CB945004, 2013CB945603)Natural Scientific Foundation of China (31125017, 31190063, 31100975, 31301149, 31471259)the 111 Project (B13026)
文摘Nuclear distribution gene C (NudC) was first found in Aspergillus nidulans as an upstream regulator of NudF, whose mamma- lian homolog is Lissencephaly 1 (Lisl). NudC is conserved from fungi to mammals. Vertebrate NudC has three homologs: NudC, NudC-like protein (NudCL), and NudC-like protein 2 (NudCL2). All members of the NudC family share a conserved p23 domain, which possesses chaperone activity both in conjunction with and independently of heat shock protein 90 (Hsp90). Our group and the others found that NudC homologs were involved in cell cycle regulation by stabilizing the components of the LIS l/dynein complex. Additionally, NudC plays important roles in cell migration, ciliogenesis, thrombopoiesis, and the in- flammatory response. It has been reported that NudCL is essential for the stability of the dynein intermediate chain and cilio- genesis via its interaction with the dynein 2 complex. Our data showed that NudCL2 regulates the LISl/dynein pathway by stabilizing LIS 1 with Hsp90 chaperone. The fourth distantly related member of the NudC family, CML66, a tumor-associated antigen in human leukemia, contains a p23 domain and appears to promote oncogenesis by regulating the IGF-1R-MAPK sig- naling pathway. In this review, we summarize our current knowledge of the NudC family and highlight its potential clinical relevance.