摘要
赖氨酸乙酰转移酶5(KAT5)作为MYST家族中的一员,可通过乙酰化不同底物,参与转录、DNA修复、分化和信号转导等细胞过程。KAT5的作用不可被其他MYST家族成员替代,并且KAT 5的敲除可直接导致细胞凋亡,说明KAT5可能位于细胞中生理信号通路的上游,发挥着极其重要且独一无二的作用。因此,KAT5表达量的变化极有可能导致肿瘤的发生发展。过去的研究发现,KAT5在乳腺癌、黑色素瘤、肺癌中表达降低,在这些肿瘤中被认为是抑癌因子。然而,近年来研究发现,KAT5在乳腺癌、肝癌、黑色素瘤、前列腺癌和肺癌等肿瘤中既可高表达又可低表达。在KAT5高表达前提下,KAT5可作为促癌因子发挥促癌作用,而在KAT5低表达的前提下,KAT5又可作为抑癌因子发挥抑癌作用,并随着KAT5进一步表达下降,抑癌作用减弱,从而导致肿瘤的发生发展。此外,KAT5还被发现在骨肉瘤、甲状腺癌、胶质母细胞瘤和结直肠癌等肿瘤中异常表达,且KAT5的异常表达与肿瘤细胞的增殖、转移、凋亡、药物和放疗抵抗性密切相关。因此,KAT5是具有潜力的肿瘤治疗靶点之一。本文根据近些年KAT5在肿瘤中的表达量和在相应表达量下参与的抑癌或促癌信号通路进行综述,希望为肿瘤的治疗与预后监测提供新的启示和参考。
Lysine acetyltransferase 5(KAT5),a member of the MYST family,can participate in cellular processes such as transcription,DNA repair,differentiation and signal transduction by acetylating different substrates.The role of KAT5 cannot be replaced by other MYST family members,and the knockout of KAT5 can directly lead to apoptosis,indicating that KAT5 may be located in the upstream of physiological signaling pathways in cells and play an extremely important and unique role.Therefore,the changes in KAT5 expression are very likely to lead to the occurrence and development of tumors.Previous studies have found that KAT5 is downregulated in breast cancer,melanoma,and lung cancer,and is considered a tumor suppressor in these tumors.However,in recent years,studies have found that KAT5 can be either highly or lowly expressed in breast cancer,liver cancer,melanoma,prostate cancer,lung cancer and other tumors.On the premise of high KAT5 expression,KAT5 can play a tumor-promoting role.While on the premise of low KAT5 expression,KAT5 can also play as a tumor suppressor.With further decrease of KAT5 expression,its tumor suppressive effect is weakened,which may lead to the occurrence and development of tumors.In addition,KAT5 has also been found to be differentially expressed in osteosarcoma,thyroid cancer,glioblastoma,colorectal cancer and other tumors,and the differential expression of KAT5 is closely related to the proliferation,metastasis,apoptosis,drug and radiotherapy resistance of tumor cells.Therefore,KAT5 is one of the potential tumor therapeutic targets.Here,we summarize the expression of KAT5 in tumors and the tumor-suppressing or tumor-promoting signaling pathways involved in the corresponding expression in recent years,hoping to provide new inspiration and reference for tumor treatment and prognosis monitoring.
作者
艾明发
金燕
张子波
AI Ming-Fa;JIN Yan;ZHANG Zi-Bo(Department of Cell Biology and Medical Genetics,College of Medicine,Yanbian University,Yanji 133002,Jilin,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2022年第8期1023-1032,共10页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金项目(No.81660494)资助。
关键词
赖氨酸乙酰转移酶5
乙酰化
肿瘤发生
促癌作用
抑癌作用
lysine acetyltransferase 5(KAT5)
acetylation
tumorigenesis
tumor-promoting effect
tumor-suppressing effect
