JNK is a key regulator of many cellular events, including programmed cell death (apoptosis). In the absence of NF- κB activation, prolonged JNK activation contributes to TNF-α induced apoptosis. JNK is also essentia...JNK is a key regulator of many cellular events, including programmed cell death (apoptosis). In the absence of NF- κB activation, prolonged JNK activation contributes to TNF-α induced apoptosis. JNK is also essential for UV induced apoptosis. However, recent studies reveal that JNK can suppress apoptosis in IL-3-dependent hematopoietic cells via phosphorylation of the proapoptotic Bcl-2 family protein BAD. Thus, JNK has pro- or antiapoptotic functions, depend- ing on cell type, nature of the death stimulus, duration of its activation and the activity of other signaling pathways.展开更多
NF-κB is thought of as a genetic switch to control expressions of many target genes and directly participates in pathogenesis of infection, inflammation, stress, immunoresponse, cellular apoptosis, toxic shock and tu...NF-κB is thought of as a genetic switch to control expressions of many target genes and directly participates in pathogenesis of infection, inflammation, stress, immunoresponse, cellular apoptosis, toxic shock and tumor as well as cell-cycle regulation and cell differentiation. The overactivation of NF-κB is intimately involved in many human diseases. Various therapeutic strategies against NF-κB, to date, include anti-inflammatory drugs, antioxidants, immunosuppressive agents, inhibitors of protease and proteasome, prostaglandings, nitric oxide, IL-10, microbial products, synthetic inhibitors, antisense oligonucleotides and decoy deoxyoligonucleotides. Studies are underway to develop NF-κB member-specific and cell type-specific drugs that can inhibit the activation of NF-κB only in target cells and that may become a novel way to treat the human diseases.展开更多
Although links between cancer and inflammation were fi rstly proposed in the nineteenth century,the molecular mechanism has not yet been clearly understood.Epidemiological studies have identified chronic infections an...Although links between cancer and inflammation were fi rstly proposed in the nineteenth century,the molecular mechanism has not yet been clearly understood.Epidemiological studies have identified chronic infections and infl ammation as major risk factors for various types of cancer.NF-κB transcription factors and the signaling pathways are central coordinators in innate and adaptive immune responses.STAT3 regulates the expression of a variety of genes in response to cellular stimuli,and thus plays a key role in cell growth and apoptosis.Recently,roles of NF-κB and STAT3 in colon,gastric and liver cancers have been extensively investigated.The activation and interaction between STAT3 and NF-κB play vital roles in control of the communication between cancer cells and infl ammatory cells.NF-κB and STAT3 are two major factors controlling the ability of pre-neoplastic and malignant cells to resist apoptosis-based tumor-surveillance and regulating tumor angiogenesis and invasiveness.Understanding the molecular mechanisms of NF-κB and STAT3 cooperation in cancer will offer opportunities for the design of new chemo-preventive and chemotherapeutic approaches.展开更多
Janus kinase-signal transduction and transcription activator (JAK-STAT), mitogen- activated protein kinase (MAPK) and nuclear factor κB (NF-κB) are three important cellular signalling pathways, which play pivotal ro...Janus kinase-signal transduction and transcription activator (JAK-STAT), mitogen- activated protein kinase (MAPK) and nuclear factor κB (NF-κB) are three important cellular signalling pathways, which play pivotal roles in regulation of cellular physiologic as well as pathophysiologic functions. Based on the elucidation of the research progress of three signalling cascades, respectively, the current review focuses on the cross-talk of these signalling transduction, and the up-to-date details are also presented on their regulation in inflammatory response.展开更多
文摘JNK is a key regulator of many cellular events, including programmed cell death (apoptosis). In the absence of NF- κB activation, prolonged JNK activation contributes to TNF-α induced apoptosis. JNK is also essential for UV induced apoptosis. However, recent studies reveal that JNK can suppress apoptosis in IL-3-dependent hematopoietic cells via phosphorylation of the proapoptotic Bcl-2 family protein BAD. Thus, JNK has pro- or antiapoptotic functions, depend- ing on cell type, nature of the death stimulus, duration of its activation and the activity of other signaling pathways.
文摘NF-κB is thought of as a genetic switch to control expressions of many target genes and directly participates in pathogenesis of infection, inflammation, stress, immunoresponse, cellular apoptosis, toxic shock and tumor as well as cell-cycle regulation and cell differentiation. The overactivation of NF-κB is intimately involved in many human diseases. Various therapeutic strategies against NF-κB, to date, include anti-inflammatory drugs, antioxidants, immunosuppressive agents, inhibitors of protease and proteasome, prostaglandings, nitric oxide, IL-10, microbial products, synthetic inhibitors, antisense oligonucleotides and decoy deoxyoligonucleotides. Studies are underway to develop NF-κB member-specific and cell type-specific drugs that can inhibit the activation of NF-κB only in target cells and that may become a novel way to treat the human diseases.
基金supported by the NIH/NINDS grant 1R01NS072420-01.
文摘Although links between cancer and inflammation were fi rstly proposed in the nineteenth century,the molecular mechanism has not yet been clearly understood.Epidemiological studies have identified chronic infections and infl ammation as major risk factors for various types of cancer.NF-κB transcription factors and the signaling pathways are central coordinators in innate and adaptive immune responses.STAT3 regulates the expression of a variety of genes in response to cellular stimuli,and thus plays a key role in cell growth and apoptosis.Recently,roles of NF-κB and STAT3 in colon,gastric and liver cancers have been extensively investigated.The activation and interaction between STAT3 and NF-κB play vital roles in control of the communication between cancer cells and infl ammatory cells.NF-κB and STAT3 are two major factors controlling the ability of pre-neoplastic and malignant cells to resist apoptosis-based tumor-surveillance and regulating tumor angiogenesis and invasiveness.Understanding the molecular mechanisms of NF-κB and STAT3 cooperation in cancer will offer opportunities for the design of new chemo-preventive and chemotherapeutic approaches.
文摘Janus kinase-signal transduction and transcription activator (JAK-STAT), mitogen- activated protein kinase (MAPK) and nuclear factor κB (NF-κB) are three important cellular signalling pathways, which play pivotal roles in regulation of cellular physiologic as well as pathophysiologic functions. Based on the elucidation of the research progress of three signalling cascades, respectively, the current review focuses on the cross-talk of these signalling transduction, and the up-to-date details are also presented on their regulation in inflammatory response.
