AMOT家族成员的功能研究及在癌症治疗中的潜在应用<sup>*</sup>

doi:10.13523/j.cb.2209072

中国生物工程杂志

2023, Vol. 43

Issue (2/3): 104-119 DOI: 10.13523/j.cb.2209072

综述

AMOT家族成员的功能研究及在癌症治疗中的潜在应用^*

张鑫^1,^2,^3,⁴,张瑞^1,^2,^3,^4,^**(

),唐景峰^1,^2,^3,^4,^**(

)

1 湖北工业大学科技部/教育部细胞调控与分子药物学科“111”引智基地武汉 430068
2 湖北工业大学发酵工程教育部重点实验室武汉 430068
3 湖北工业大学工业发酵省部共建协同创新中心武汉 430068
4 湖北工业大学工业微生物湖北省重点实验室武汉 430068

Functional Studies of AMOT Family Members and Their Potential Applications in Cancer Therapy

ZHANG Xin^1,^2,^3,⁴,ZHANG Rui^1,^2,^3,^4,^**(

),TANG Jing-feng^1,^2,^3,^4,^**(

)

1 National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, China
2 Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China
3 Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei University of Technology, Wuhan 430068, China
4 Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan 430068, China

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摘要：

AMOT是一种血管生成抑制素的结合蛋白。AMOT家族(AMOTs)成员参与调控细胞增殖、细胞迁移、血管生成、病毒释放等重要的细胞生物学过程。AMOTs在多数癌细胞中表达,并参与癌症的发生和进程。现有证据表明AMOTs在癌症进程中扮演双重角色,既是癌症促进因子,也是癌症抑制因子。AMOTs在癌症中的这种双重调控机制尚且存在争议。重点阐明了AMOTs的结构特征、表达定位、翻译后修饰和生物学功能,系统概述了AMOTs在癌症中的研究现状及治疗潜力,讨论了通过AMOTs治疗癌症的可能性和面临的挑战。

关键词： AMOT家族; 生物学功能; 癌症; 治疗靶点

Abstract:

Angiomotin(AMOT) is a type of angiogenesis inhibitor binding protein. Members of the AMOT family (AMOTs) are involved in various critical biological processes, for example, cell proliferation, cell migration, angiogenesis, and virus release. AMOTs expressed in most cancer and regulate cancer development and progression. Available evidence suggests that AMOTs act as both tumor promoters and tumor suppressors, and this opposite regulation in cancer still needs to be validated. This review focuses on the structure, expression localization, and function of AMOTs, and additionally, it systematically summarizes previous research and therapeutic roles in cancer. It discusses the possibility and challenges of treating cancer through AMOTs.

Key words: Angiomotin family Biological functions Cancer Therapeutic target

收稿日期: 2022-09-27 出版日期: 2023-03-31

ZTFLH:

Q819

基金资助: *国家自然科学基金(32000523);国家自然科学基金(32070726);湖北省科技厅自然科学基金(2020CFB413)

通讯作者: **张瑞,唐景峰 E-mail: zhangrui1987@hbut.edu.cn;tangjingfeng@hbut.edu.com

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引用本文:

张鑫, 张瑞, 唐景峰. AMOT家族成员的功能研究及在癌症治疗中的潜在应用^*[J]. 中国生物工程杂志, 2023, 43(2/3): 104-119.

ZHANG Xin, ZHANG Rui, TANG Jing-feng. Functional Studies of AMOT Family Members and Their Potential Applications in Cancer Therapy. China Biotechnology, 2023, 43(2/3): 104-119.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2209072 或 https://manu60.magtech.com.cn/biotech/CN/Y2023/V43/I2/3/104

图1 AMOT蛋白家族各成员结构域的示意图

图2 AMOT蛋白家族各成员在不同人体组织中的mRNA表达水平(研究结果来自人类蛋白质图谱数据库)

AMOT家族	相互作用蛋白	结构域或基序	可能的功能	参考文献
AMOT	YAP1/TAZ/AIP4	L/PPxY基序	调节细胞增殖和癌症发展	[40,54]
	14-3-3	RSLSERLMQ	胞质滞留	[55]
	LATS1/2	HVRSLS	磷酸化、刺激LATS激酶自磷酸化	[34,52]
	Merlin/RICK	Colied-coil结构域	调节细胞迁移和细胞连接	[54]
	Patj	PDZ 结合基序	调节细胞迁移和细胞连接	[54]
	RICH1	Colied-coil结构域	激活Hippo信号	[17]
	WWOX	L/PPxY基序	调节丝状病毒VP40 VLPs的排出	[56]
	F-actin	F-actin结合基序	调节YAP定位	[19]
	KIF13B	未知	调节纤毛长度、成分和信号	[57]
	NEDD4L	L/PPxY基序	刺激HIV-1包膜并促进传染性	[18]
	eIF4A	238~255氨基酸	限制球蛋白质合成	[58]
	UCA1	Colied-coil结构域	促进YAP去磷酸化和核易位	[6]
	RNF146/TNKS	N-terminal结构域	调节β-catenin的稳定性;维持细胞连接处的Crumbs复合体	[49,59]
	PAR6	PDZ 结合基序	通过细胞极性变化促进细胞迁移	[2]
	BMPR2/SMAD1	未知	调节BMP靶基因表达	[60]
	MUPP1/PSD-95	未知	控制肌动蛋白周转和PSD完整性	[61]
	Rho	Colied-coil结构域	调节AMOT的分布和磷酸化	[62]
AMOT家族	相互作用蛋白	结构域或基序	可能的功能	参考文献
	TFPI-1	未知	激活Hippo信号	[63]
	PKCι	Colied-coil结构域	磷酸化和调节核YAP定位	[36]
	USP9X	Colied-coil结构域	脱乙酰基化	[40]
	Par/Crb	PDZ结合基序	内分泌循环	[64]
	sCD146	未知	促进血管生成	[65]
	Cad11	Middle domain	细胞迁移	[53]
	NEDD4/ITCH	L/PPxY基序	泛素化	[41]
	CDH1	未知	激活LATS1/2	[66]
AMOTL1	LATS1/2	HVRSLS	磷酸化	[34]
	YAP1	L/PPxY基序	增加YAP稳定性	[67]
	PIV5 M	C-terminal结构域	调节副黏病毒出芽	[46]
	NEDD4L/ NEDD4/ HECW1	L/PPxY基序	泛素化;招募副黏病毒M蛋白	[46]
	USP9X	Colied-coil结构域	去泛素化	[40]
	RNF146/TNKS	N-terminal结构域	维持细胞连接处的Crumbs复合体	[49]
	N-cadherin	未知	影响血管生成	[68]
	Fat4	未知	介导Fat4信号转导	[30]
	AMPK	Ser793	磷酸化	[37]
	HECW2	L/PPxY基序	泛素化	[44]
AMOTL2	LATS1/2	HVRSLS	磷酸化	[34]
	Par3	未知	调节细胞连接定位	[69]
	USP9X	Colied-coil结构域	去泛素化	[40]
	RNF146/TNKS	N-terminal结构域	维持细胞连接处的Crumbs复合体	[49]
	β-catenin	Colied-coil/ N-terminal 结构域	抑制Wnt/β-catenin信号	[70]
	mTORC2	402~512 氨基酸	磷酸化	[38]
	c-Src	未知	调节易位	[71]
	WWP1	L/PPxY基序	泛素化	[42]
	PPP2R2A	1~103 氨基酸	抑制JUN Thr239去磷酸化	[72]
	LL5β	未知	未知	[73]
	AKT	未知	抑制AKT信号	[74]

表1 AMOTs的互作蛋白、相应的结合结构域和功能。

表2 AMOTs在不同癌症中的作用及可能的调控机制。

图3 AMOT相关分子机制示意图

图4 AMOTL1和AMOTL2的部分相关分子机制示意图

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