目的:探讨TPMT*2 rs1800462 C > G;TPMT*3C rs1142345 T > C;NUDT15rs116855232 C > T基因多态性对急性淋巴细胞白血病(ALL)患儿6-巯基嘌呤(6-MP)耐受性的影响。方法:选取2019年3月-2024年12月于本院儿血液肿瘤科诊断并接受治...目的:探讨TPMT*2 rs1800462 C > G;TPMT*3C rs1142345 T > C;NUDT15rs116855232 C > T基因多态性对急性淋巴细胞白血病(ALL)患儿6-巯基嘌呤(6-MP)耐受性的影响。方法:选取2019年3月-2024年12月于本院儿血液肿瘤科诊断并接受治疗的53例ALL患儿,应用6-MP治疗前检测患儿的TPMT、NUDT15基因型。收集患儿的临床资料及实验室检测结果,分析基因多态性对维持治疗期间6-MP耐受性的影响。结果:53例ALL患儿中,TPMT*2rs1800462 C > G:CC型53例(100%);TPMT*3C rs1142345 T > C:TT型49例(92.45%)、TC型3例(5.66%)、CC型1例(1.89%),等位基因突变频率4.72%;NUDT15 rs116855232 C > T:CC型39例(73.58%)、CT型11例(20.75%)、TT型3例(5.66%),等位基因突变频率为16.03%。维持治疗期间,NUDT15 rs116855232 TT型患儿白细胞、中性粒细胞绝对值、血红蛋白、血小板计数均低于其他组。CC型、CT型和TT型患儿6-MP耐受日剂量分别为(43.8±10.5)mg·m^(-2)、(27.4±9.1)mg·m^(-2)和(4.5±0.7)mg·m^(-2)。结论:NUDT15基因多态性可以影响ALL患儿对6-MP的耐受性。治疗前行6-MP药物基因检测,可根据基因型调整6-MP的剂量,为临床医生提供用药方案建议。展开更多
Messenger RNA(mRNA)translation consists of initiation,elongation,termination,and ribosome recycling,carried out by the translation machinery,primarily including tRNAs,ribosomes,and translation factors(TrFs).Translatio...Messenger RNA(mRNA)translation consists of initiation,elongation,termination,and ribosome recycling,carried out by the translation machinery,primarily including tRNAs,ribosomes,and translation factors(TrFs).Translational regulators transduce signals of growth and development,as well as biotic and abiotic stresses,to the translation machinery,where global or selective translational control occurs to modulate mRNA translation efficiency(TrE).As the basis of translational control,the translation machinery directly determines the quality and quantity of newly synthesized peptides and,ultimately,the cellular adaption.Thus,regulating the availability of diverse machinery components is reviewed as the central strategy of translational control.We provide classical signaling pathways(e.g.,integrated stress responses)and cellular behaviors(e.g.,liquideliquid phase separation)to exemplify this strategy within different physiological contexts,particularly during hostemicrobe interactions.With new technologies developed,further understanding this strategy will speed up translational medicine and translational agriculture.展开更多
Protein post-translational modifications(PTMs),such as ubiquitination,phosphorylation,and small ubiquitin-like modifier(SUMO)ylation,are crucial for regulating protein stability,activity,subcellular localization,and b...Protein post-translational modifications(PTMs),such as ubiquitination,phosphorylation,and small ubiquitin-like modifier(SUMO)ylation,are crucial for regulating protein stability,activity,subcellular localization,and binding with cofactors.Such modifications remarkably increase the variety and complexity of proteomes,which are essential for regulating numerous cellular and physiological processes.The regulation of auxin signaling is finely tuned in time and space to guide various plant growth and development.Accumulating evidence indicates that PTMs play critical roles in auxin signaling regulations.Thus,a thorough and systematic review of the functions of PTMs in auxin signal transduction will improve our profound comprehension of the regulation mechanism of auxin signaling and auxin-mediated various processes.This review discusses the progress of protein ubiquitination,phosphorylation,histone acetylation and methylation,SUMOylation,and S-nitrosylation in the regulation of auxin signaling.展开更多
The generation of mature and healthy oocytes is the most critical event in the entire female reproductive process,and the mechanisms regulating this process remain to be studied.Here,we demonstrate that Smith-like(LSM...The generation of mature and healthy oocytes is the most critical event in the entire female reproductive process,and the mechanisms regulating this process remain to be studied.Here,we demonstrate that Smith-like(LSM)family member 14B(LSM14B)regulates oocyte maturation,and the loss of LSM14B in mouse ovaries leads to abnormal oocyte MII arrest and female infertility.Next,we find the aberrant transcriptional activation,indicated by abnormal non-surrounded nucleolus and surrounded nucleolus oocyte proportions,and abnormal chromosome assembly and segregation in Lsm14b-deficient mouse oocytes.The global transcriptome analysis suggests that many transcripts involved in cytoplasmic processing body(P-body)function are altered in Lsm14b-deficient mouse oocytes.Deletion of Lsm14b results in the expression and/or localization changes of P-body components(such as LSM14A,DCP1A,and 4E-T).Notably,DDX6,a key component of the P-body,is downregulated and accumulates in the nuclei in Lsm14b-deficient mouse oocytes.Taken together,our data suggest that LSM14B links mouse oocyte maturation to female fertility through the regulation of the P-body.展开更多
文摘目的:探讨TPMT*2 rs1800462 C > G;TPMT*3C rs1142345 T > C;NUDT15rs116855232 C > T基因多态性对急性淋巴细胞白血病(ALL)患儿6-巯基嘌呤(6-MP)耐受性的影响。方法:选取2019年3月-2024年12月于本院儿血液肿瘤科诊断并接受治疗的53例ALL患儿,应用6-MP治疗前检测患儿的TPMT、NUDT15基因型。收集患儿的临床资料及实验室检测结果,分析基因多态性对维持治疗期间6-MP耐受性的影响。结果:53例ALL患儿中,TPMT*2rs1800462 C > G:CC型53例(100%);TPMT*3C rs1142345 T > C:TT型49例(92.45%)、TC型3例(5.66%)、CC型1例(1.89%),等位基因突变频率4.72%;NUDT15 rs116855232 C > T:CC型39例(73.58%)、CT型11例(20.75%)、TT型3例(5.66%),等位基因突变频率为16.03%。维持治疗期间,NUDT15 rs116855232 TT型患儿白细胞、中性粒细胞绝对值、血红蛋白、血小板计数均低于其他组。CC型、CT型和TT型患儿6-MP耐受日剂量分别为(43.8±10.5)mg·m^(-2)、(27.4±9.1)mg·m^(-2)和(4.5±0.7)mg·m^(-2)。结论:NUDT15基因多态性可以影响ALL患儿对6-MP的耐受性。治疗前行6-MP药物基因检测,可根据基因型调整6-MP的剂量,为临床医生提供用药方案建议。
基金supported by grants from the National Natural Science Foundation of China(32070284)the Major Project of Hubei Hongshan Laboratory(2022hszd016)the Key Research and Development Program of Hubei Province(2022BFE003)to G.Xu.We apologize to colleagues whose excellent work was not cited in this review due to the space limit.
文摘Messenger RNA(mRNA)translation consists of initiation,elongation,termination,and ribosome recycling,carried out by the translation machinery,primarily including tRNAs,ribosomes,and translation factors(TrFs).Translational regulators transduce signals of growth and development,as well as biotic and abiotic stresses,to the translation machinery,where global or selective translational control occurs to modulate mRNA translation efficiency(TrE).As the basis of translational control,the translation machinery directly determines the quality and quantity of newly synthesized peptides and,ultimately,the cellular adaption.Thus,regulating the availability of diverse machinery components is reviewed as the central strategy of translational control.We provide classical signaling pathways(e.g.,integrated stress responses)and cellular behaviors(e.g.,liquideliquid phase separation)to exemplify this strategy within different physiological contexts,particularly during hostemicrobe interactions.With new technologies developed,further understanding this strategy will speed up translational medicine and translational agriculture.
基金supported by the National Natural Science Foundation of China(32061143005,32170313,and 32100266)Shandong Provincial Natural Science Foundation(ZR2021QC022 and ZR2022QC059).
文摘Protein post-translational modifications(PTMs),such as ubiquitination,phosphorylation,and small ubiquitin-like modifier(SUMO)ylation,are crucial for regulating protein stability,activity,subcellular localization,and binding with cofactors.Such modifications remarkably increase the variety and complexity of proteomes,which are essential for regulating numerous cellular and physiological processes.The regulation of auxin signaling is finely tuned in time and space to guide various plant growth and development.Accumulating evidence indicates that PTMs play critical roles in auxin signaling regulations.Thus,a thorough and systematic review of the functions of PTMs in auxin signal transduction will improve our profound comprehension of the regulation mechanism of auxin signaling and auxin-mediated various processes.This review discusses the progress of protein ubiquitination,phosphorylation,histone acetylation and methylation,SUMOylation,and S-nitrosylation in the regulation of auxin signaling.
基金supported by the National Key R&D Program of China(2021YFC2700201 to X.W.)the National Natural Science Foundation of China(32070831,32270897 to X.W.).
文摘The generation of mature and healthy oocytes is the most critical event in the entire female reproductive process,and the mechanisms regulating this process remain to be studied.Here,we demonstrate that Smith-like(LSM)family member 14B(LSM14B)regulates oocyte maturation,and the loss of LSM14B in mouse ovaries leads to abnormal oocyte MII arrest and female infertility.Next,we find the aberrant transcriptional activation,indicated by abnormal non-surrounded nucleolus and surrounded nucleolus oocyte proportions,and abnormal chromosome assembly and segregation in Lsm14b-deficient mouse oocytes.The global transcriptome analysis suggests that many transcripts involved in cytoplasmic processing body(P-body)function are altered in Lsm14b-deficient mouse oocytes.Deletion of Lsm14b results in the expression and/or localization changes of P-body components(such as LSM14A,DCP1A,and 4E-T).Notably,DDX6,a key component of the P-body,is downregulated and accumulates in the nuclei in Lsm14b-deficient mouse oocytes.Taken together,our data suggest that LSM14B links mouse oocyte maturation to female fertility through the regulation of the P-body.
