受体相互作用蛋白激酶1(receptor-interacting protein kinase 1,RIPK1)是一种多结构域丝氨酸/苏氨酸蛋白激酶。它通过磷酸化特定的蛋白质,引起下游的信号转导和生物效应。近年来,随着对RIPK1的深入研究,学者发现其在自身免疫性疾病、...受体相互作用蛋白激酶1(receptor-interacting protein kinase 1,RIPK1)是一种多结构域丝氨酸/苏氨酸蛋白激酶。它通过磷酸化特定的蛋白质,引起下游的信号转导和生物效应。近年来,随着对RIPK1的深入研究,学者发现其在自身免疫性疾病、神经退行性疾病,以及多种实体瘤和血液肿瘤中具有重要意义。一方面,RIPK1通过激活特定通路如核因子-κB(nuclear factor-κB,NF-κB)和丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等促进细胞存活及炎症反应。另一方面,RIPK1通过与胱天蛋白酶-8(cysteinyl aspartate specific proteinase-8,caspase-8)作用促进凋亡,或与RIPK3和混合谱系激酶结构域样假激酶(mixed lineage kinase domain-like protein,MLKL)作用促进坏死性凋亡的发生。RIPK1作为上游信号在不同肿瘤患者中表达水平不同。其支架功能和激酶活性可以调节癌症进展,也可以启动机体适应性免疫,抑制肿瘤进展;此外,还能产生免疫抑制性肿瘤微环境而促进肿瘤的发展。其双重作用在调节癌症的发生、发展及机体免疫反应方面都有所展现,可以作为新的治疗靶点控制癌症进展。该文从RIPK1的结构入手,深入探讨其功能,特别是其在调节癌症进展和免疫反应方面的功能,为癌症靶向药物的开发提供新的思路。展开更多
In order to explore the functions of retinol binding protein (RBP4) in regulation of gene expression, yeast two hybrid assay and transient co-transforming were used to detect the interactions between RBP4 and nuclear ...In order to explore the functions of retinol binding protein (RBP4) in regulation of gene expression, yeast two hybrid assay and transient co-transforming were used to detect the interactions between RBP4 and nuclear receptors and the effects of over-expressed RBP4 on trans-activation functions of human estrogen receptor related receptor 1 (hERR1) and human estrogen (hER). The requirement of activation function domain-2 (AF-2) for hER to interact with RBP4 was also detected by the yeast two hybrid assay. The results show that RBP4 could interact with many nuclear receptors including mouse estrogen receptor related receptor 3 (mERR3), retinoid X receptor (RXR), glucocorticoid receptor (GR), progestin receptor (PR), and androgen receptor (AR) in yeast cells. Over-expressed RBP4 could strongly enhance the trans-activation functions of hERR1 and hER in a dose-dependent manner, respectively. RBP4 could also interact with hER in an AF-2-dependent manner.展开更多
文摘受体相互作用蛋白激酶1(receptor-interacting protein kinase 1,RIPK1)是一种多结构域丝氨酸/苏氨酸蛋白激酶。它通过磷酸化特定的蛋白质,引起下游的信号转导和生物效应。近年来,随着对RIPK1的深入研究,学者发现其在自身免疫性疾病、神经退行性疾病,以及多种实体瘤和血液肿瘤中具有重要意义。一方面,RIPK1通过激活特定通路如核因子-κB(nuclear factor-κB,NF-κB)和丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等促进细胞存活及炎症反应。另一方面,RIPK1通过与胱天蛋白酶-8(cysteinyl aspartate specific proteinase-8,caspase-8)作用促进凋亡,或与RIPK3和混合谱系激酶结构域样假激酶(mixed lineage kinase domain-like protein,MLKL)作用促进坏死性凋亡的发生。RIPK1作为上游信号在不同肿瘤患者中表达水平不同。其支架功能和激酶活性可以调节癌症进展,也可以启动机体适应性免疫,抑制肿瘤进展;此外,还能产生免疫抑制性肿瘤微环境而促进肿瘤的发展。其双重作用在调节癌症的发生、发展及机体免疫反应方面都有所展现,可以作为新的治疗靶点控制癌症进展。该文从RIPK1的结构入手,深入探讨其功能,特别是其在调节癌症进展和免疫反应方面的功能,为癌症靶向药物的开发提供新的思路。
文摘In order to explore the functions of retinol binding protein (RBP4) in regulation of gene expression, yeast two hybrid assay and transient co-transforming were used to detect the interactions between RBP4 and nuclear receptors and the effects of over-expressed RBP4 on trans-activation functions of human estrogen receptor related receptor 1 (hERR1) and human estrogen (hER). The requirement of activation function domain-2 (AF-2) for hER to interact with RBP4 was also detected by the yeast two hybrid assay. The results show that RBP4 could interact with many nuclear receptors including mouse estrogen receptor related receptor 3 (mERR3), retinoid X receptor (RXR), glucocorticoid receptor (GR), progestin receptor (PR), and androgen receptor (AR) in yeast cells. Over-expressed RBP4 could strongly enhance the trans-activation functions of hERR1 and hER in a dose-dependent manner, respectively. RBP4 could also interact with hER in an AF-2-dependent manner.
