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作 者:诸葛瑞鹏 黄新平 郑晓峰[1] ZHUGE Rui-Peng;HUANG Xin-Ping;ZHENG Xiao-Feng(School of Life Sciences,Peking University,Beijing 100871,China)
出 处:《生物化学与生物物理进展》2023年第5期1122-1132,共11页Progress In Biochemistry and Biophysics
基 金:国家自然科学基金(32270756)资助项目。
摘 要:腺苷酸激酶广泛存在于各种生物中,在维持细胞中核苷酸的正常含量以及能量代谢活动中发挥重要作用。腺苷酸激酶6 (AK6,又称人coilin相互作用核ATP酶蛋白hCINAP)是一种非典型的腺苷酸激酶,既具有腺苷酸激酶的活性,又具有ATP酶的活性。本课题组对AK6/hCINAP的结构、酶学特征和生物学功能开展了长期的研究,证明其在调控基因转录、核糖体质量、早期胚胎发育、细胞衰老、细胞代谢、细胞增殖和凋亡、DNA损伤反应、炎症反应、肿瘤发展等诸多生物学过程中均发挥关键作用。本文对AK6/hCINAP的结构特征、生物学功能及上游调控因子进行了总结,阐明该酶生物学作用和分子机制具有重要的生物学意义,有助于开发AK6/hCINAP选择性抑制剂并应用于临床治疗。Adenylate kinases(AK)are widely existing in various organisms,which play critical roles in maintaining the normal content of nucleotides and regulation of energy metabolism in cells.Among AK family members,AK6,also known as human coilin-interacting nuclear ATPase protein(hCINAP),is an atypical adenylate kinase that possesses both activities of adenylate kinase and ATPase.We have been carried out longterm research on the structure,enzymatic activity and functions of this enzyme,and demonstrated that AK6/hCINAP plays critical roles in many biological processes,including gene transcription,ribosome quality control,embryonic development,senescence,cell metabolism,cell proliferation and apoptosis,DNA damage responses,inflammatory response,and tumor development.In this review,we summarize the structural features,biological roles and transcriptional regulators of AK6/hCINAP,which provides important insights into its activity and functions,and contributes to the screening of specific inhibitors of AK6/hCINAP and its application in clinical therapy in the future.
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