摘要
植物同源域锌指蛋白5A(PHF5A)是PHD-finger样蛋白超家族成员之一,广泛表达于真核生物细胞核中,其PHD-finger样结构域是蛋白质-DNA或蛋白质-蛋白质相互作用区。PHF5A除作为剪接体蛋白组成亚单位调控靶基因的选择性剪接外,还在胚胎干细胞的多潜能性维持、染色质结构重塑、DNA损伤修复、胚胎形成与组织形态发育等方面发挥重要作用。近年来,越来越多的研究集中在探索PHF5A的剪接体相关功能和非剪接体相关功能,及其功能异常与乳腺癌、肺癌、结直肠癌等多种恶性肿瘤的发生、发展及预后的关系,并发现其潜在机制可能包括介导靶基因的异常选择性剪接、作为原癌基因/蛋白激活下游信号通路、作为核转录因子或辅因子调控异常的基因转录等。此外,PHF5A还参与某些肿瘤干细胞的生长调控。本文就PHF5A的结构及功能特点及其在多种恶性肿瘤发生发展中的作用进行综述,以期为抗肿瘤治疗提供潜在作用靶点。
PHD-finger domain protein 5A(PHF5A)is a member of the PHD-finger like protein superfamily and widely expressed in the nucleus of eukaryotes.The PHD-finger like domain is a protein-DNA or protein-protein interaction region.In addition to regulate alternative splicing of target genes as a spliceosome protein subunit,PHF5A is also involved in pluripotency maintenance of embryonic stem cells,chromatin remodeling,DNA damage repair,embryogenesis and histomorphological development.Recently,increasing studies have focused on exploring spliceosome-related and non-spliceosome-related functions of PHF5A and its relationship with the tumorigenesis,development and patient prognosis of various malignant tumors,such as breast cancer,lung cancer and colorectal cancer.The underlying mechanisms of PHF5A may include mediating aberrant alternative splicing of target genes,activating downstream signaling pathways as an oncogene/protein,and regulating abnormal gene transcription as a nuclear transcription factor or cofactor.Besides,PHF5A was also found to be involved in the growth regulation of cancer stem cells.In this review,we aimed to delineate the structural and functional characteristics of PHF5A,to summarize its role in the occurrence and development of malignant tumors hitherto described,and to provide potential targets for anti-tumor therapy.
作者
李曼
程倩倩
王效静
杨燕
LI Man;CHENG Qianqian;WANG Xiaojing;YANG Yan(Department of Medical Oncology,the First Affiliated Hospital of Bengbu Medical College,Bengbu 233004,Anhui Province,China;Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease,Bengbu 233004,Anhui Province,China;Molecular Diagnosis Center,Department of Pulmonary and Critical Care Medicine,the First Affiliated Hospital of Bengbu Medical College,Bengbu 233004,Anhui Province,China)
出处
《浙江大学学报（医学版）》
CAS
CSCD
北大核心
2022年第5期647-655,共9页
Journal of Zhejiang University(Medical Sciences)
基金
国家自然科学基金(82072585)
安徽省自然科学基金(2008085MH238)
安徽省高校优秀青年人才支持计划(gxyq2022042)
蚌埠医学院研究生科研创新计划(Byycx20046)。
