目的建立过表达Src羧基末端激酶结合蛋白(CBP)的T系白血病Jurkat细胞动物模型。方法 5周龄雌性BALB/c-nu小鼠随机分为空白对照组、正常Jurkat细胞对照组、空病毒Jurkat细胞对照组、病毒转染过表达CBP模型组,每组5只。小鼠腋窝皮下注射Ju...目的建立过表达Src羧基末端激酶结合蛋白(CBP)的T系白血病Jurkat细胞动物模型。方法 5周龄雌性BALB/c-nu小鼠随机分为空白对照组、正常Jurkat细胞对照组、空病毒Jurkat细胞对照组、病毒转染过表达CBP模型组,每组5只。小鼠腋窝皮下注射Jurkat细胞1×107个/0.1 m L。建模成功后取出完整瘤体组织称质量、HE染色观察小鼠皮下肿块的病理变化;流式细胞术检测小鼠外周血Jurkat细胞增殖水平;ELISA检测小鼠血清中白细胞介素2(IL-2)水平。结果病毒转染过表达CBP模型组小鼠瘤体组织块体积和质量小于对照组,HE染色瘤体内有Jurkat细胞增殖,外周血Jurkat细胞增殖水平低于正常Jurkat细胞对照组和空病毒Jurkat细胞对照组,血清中IL-2水平低于正常Jurkat细胞对照组和空病毒Jurkat细胞对照组。结论成功建立了过表达CBP的Jurkat白血病细胞小鼠荷瘤模型,CBP可抑制Jurkat细胞IL-2分泌和增殖。展开更多
cAMP应答元件结合蛋白(cAMP response element binding protein,CREB)在神经元生成、突触可塑性及学习记忆等方面都具有重要的调节作用,这使得与CREB信号通路相关的分子成为较受关注的神经系统疾病干预的药物靶点.本文概述了CREB的基本...cAMP应答元件结合蛋白(cAMP response element binding protein,CREB)在神经元生成、突触可塑性及学习记忆等方面都具有重要的调节作用,这使得与CREB信号通路相关的分子成为较受关注的神经系统疾病干预的药物靶点.本文概述了CREB的基本构成、相关信号通路、其目的基因表达调控及其在阿尔茨海默病(Alzheimer’s disease,AD)中的作用.展开更多
Thymine DNA glycosylase CrDG）, an enzyme that initiates the repair of G/T and G/U mismatches, has been lately found crucial in em- bryonic development to maintain epigenetic stability and facilitate the active DNA de...Thymine DNA glycosylase CrDG）, an enzyme that initiates the repair of G/T and G/U mismatches, has been lately found crucial in em- bryonic development to maintain epigenetic stability and facilitate the active DNA demethylation. Here we report a novel role of TDG in Wnt signaling as a transcriptional coactivator of β-catenin/TCFs complex. Our data show that TDG binds to the transcriptional factor family LEF1/TCFs and potentiates β-catenin/TCFs transactivation, while TDG depletion suppresses Wnt3a-stimulated reporter activity or target gene transcription. Next, we show that CBP, a known coactivator, is also required for TDG function through forming a coopera- tive complex on target promoters. Moreover, there is an elevation of TDG levels in human colon cancer tissue, and knockdown of TDG inhibits proliferation of the colon cells. Overall, our results reveal that TDG, as a new coactivator, promotes β-catenin/TCFs transacti- vation and functionally cooperates with CBP in canonical Wnt signaUng.展开更多
文摘目的建立过表达Src羧基末端激酶结合蛋白(CBP)的T系白血病Jurkat细胞动物模型。方法 5周龄雌性BALB/c-nu小鼠随机分为空白对照组、正常Jurkat细胞对照组、空病毒Jurkat细胞对照组、病毒转染过表达CBP模型组,每组5只。小鼠腋窝皮下注射Jurkat细胞1×107个/0.1 m L。建模成功后取出完整瘤体组织称质量、HE染色观察小鼠皮下肿块的病理变化;流式细胞术检测小鼠外周血Jurkat细胞增殖水平;ELISA检测小鼠血清中白细胞介素2(IL-2)水平。结果病毒转染过表达CBP模型组小鼠瘤体组织块体积和质量小于对照组,HE染色瘤体内有Jurkat细胞增殖,外周血Jurkat细胞增殖水平低于正常Jurkat细胞对照组和空病毒Jurkat细胞对照组,血清中IL-2水平低于正常Jurkat细胞对照组和空病毒Jurkat细胞对照组。结论成功建立了过表达CBP的Jurkat白血病细胞小鼠荷瘤模型,CBP可抑制Jurkat细胞IL-2分泌和增殖。
文摘Thymine DNA glycosylase CrDG）, an enzyme that initiates the repair of G/T and G/U mismatches, has been lately found crucial in em- bryonic development to maintain epigenetic stability and facilitate the active DNA demethylation. Here we report a novel role of TDG in Wnt signaling as a transcriptional coactivator of β-catenin/TCFs complex. Our data show that TDG binds to the transcriptional factor family LEF1/TCFs and potentiates β-catenin/TCFs transactivation, while TDG depletion suppresses Wnt3a-stimulated reporter activity or target gene transcription. Next, we show that CBP, a known coactivator, is also required for TDG function through forming a coopera- tive complex on target promoters. Moreover, there is an elevation of TDG levels in human colon cancer tissue, and knockdown of TDG inhibits proliferation of the colon cells. Overall, our results reveal that TDG, as a new coactivator, promotes β-catenin/TCFs transacti- vation and functionally cooperates with CBP in canonical Wnt signaUng.
