p21Waf/Cip1, p16INK4a and p14ARF (p19ARF in mice) have been demonstrated to be degraded by REGγ-proteasome pathway in an ATP- and ubiquitin-independent manner in vitro. However, the in vivo roles of REGγ mediated-de...p21Waf/Cip1, p16INK4a and p14ARF (p19ARF in mice) have been demonstrated to be degraded by REGγ-proteasome pathway in an ATP- and ubiquitin-independent manner in vitro. However, the in vivo roles of REGγ mediated-degradation of p21Waf/Cip1, p16INK4a and p14ARF remain unclear. In this study, we showed enhanced expression of p21Waf/Cip1, p16INK4a and p19ARF in multiple tissues from REGg–/– mice compared to REGg+/+ mice. Furthermore, we examined the expression of p21Waf/Cip1, p16INK4a and p14ARF in different cancer tissues and observed that the REGγ protein levels were highly expressed in different human cancers while the level of p21Waf/Cip1, p16INK4a and p14ARF appears to be inversely correlated. These results demonstrate that REGγ may exert its function in physiological and pathological conditions through degradation of p21Waf/Cip1, p16INK4a and p14ARF in vivo.展开更多
Sepsis is a heterogeneous syndrome induced by a dysregulated host response to infection.Glycolysis plays a role in maintaining the immune function of macrophages,which is crucial for severely septic patients.However,h...Sepsis is a heterogeneous syndrome induced by a dysregulated host response to infection.Glycolysis plays a role in maintaining the immune function of macrophages,which is crucial for severely septic patients.However,how the pathways that link glycolysis and macrophages are regulated is still largely unknown.Here,we provide evidence to support the function of KLF14,a novel Krüppel-like transcription factor,in the regulation of glycolysis and the immune function of macrophages during sepsis.KLF14 deletion led to significantly increased mortality in lethal models of murine endotoxemia and sepsis.Mechanistically,KLF14 decreased glycolysis and the secretion of inflammatory cytokines by macrophages by inhibiting the transcription of HK2.In addition,we confirmed that the expression of KLF14 was upregulated in septic patients.Furthermore,pharmacological activation of KLF14 conferred protection against sepsis in mice.These findings uncover a key role of KLF14 in modulating the inflammatory signaling pathway and shed light on the development of KLF14-targeted therapeutics for sepsis.展开更多
Correction to:Cellular&Molecular Immunology https://doi.org/10.1038/s41423-021-00806-5,published online 4 January 2022 In the version of this article initially published,two unintended errors were made during manu...Correction to:Cellular&Molecular Immunology https://doi.org/10.1038/s41423-021-00806-5,published online 4 January 2022 In the version of this article initially published,two unintended errors were made during manuscript editing.The corresponding author’s name was misspelled and therefore incorrectly listed as Jingbao Li with the email address lijingbaoshanghai@163.com.展开更多
文摘p21Waf/Cip1, p16INK4a and p14ARF (p19ARF in mice) have been demonstrated to be degraded by REGγ-proteasome pathway in an ATP- and ubiquitin-independent manner in vitro. However, the in vivo roles of REGγ mediated-degradation of p21Waf/Cip1, p16INK4a and p14ARF remain unclear. In this study, we showed enhanced expression of p21Waf/Cip1, p16INK4a and p19ARF in multiple tissues from REGg–/– mice compared to REGg+/+ mice. Furthermore, we examined the expression of p21Waf/Cip1, p16INK4a and p14ARF in different cancer tissues and observed that the REGγ protein levels were highly expressed in different human cancers while the level of p21Waf/Cip1, p16INK4a and p14ARF appears to be inversely correlated. These results demonstrate that REGγ may exert its function in physiological and pathological conditions through degradation of p21Waf/Cip1, p16INK4a and p14ARF in vivo.
基金This work was supported by the National Natural Science Foundation of China(81701943,81971813).
文摘Sepsis is a heterogeneous syndrome induced by a dysregulated host response to infection.Glycolysis plays a role in maintaining the immune function of macrophages,which is crucial for severely septic patients.However,how the pathways that link glycolysis and macrophages are regulated is still largely unknown.Here,we provide evidence to support the function of KLF14,a novel Krüppel-like transcription factor,in the regulation of glycolysis and the immune function of macrophages during sepsis.KLF14 deletion led to significantly increased mortality in lethal models of murine endotoxemia and sepsis.Mechanistically,KLF14 decreased glycolysis and the secretion of inflammatory cytokines by macrophages by inhibiting the transcription of HK2.In addition,we confirmed that the expression of KLF14 was upregulated in septic patients.Furthermore,pharmacological activation of KLF14 conferred protection against sepsis in mice.These findings uncover a key role of KLF14 in modulating the inflammatory signaling pathway and shed light on the development of KLF14-targeted therapeutics for sepsis.
文摘Correction to:Cellular&Molecular Immunology https://doi.org/10.1038/s41423-021-00806-5,published online 4 January 2022 In the version of this article initially published,two unintended errors were made during manuscript editing.The corresponding author’s name was misspelled and therefore incorrectly listed as Jingbao Li with the email address lijingbaoshanghai@163.com.
