肿瘤抑制蛋白PDCD4结构特性与疾病关系解析及研究进展

doi:10.16288/j.yczz.23-291

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Hereditas(Beijing) ›› 2024, Vol. 46 ›› Issue (4): 290-305.doi: 10.16288/j.yczz.23-291

• Review • Previous Articles Next Articles

Progress on the relationship between tumor suppressor PDCD4 and diseases based on the analysis of structural characteristics

Hui Li¹(), Guangming Wu²^,³()

1. Chongqing College of Electronic Engineering, Smart Health College, Chongqing 401331, China
2. The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China
3. Division of Basic Research, Guangzhou National Laboratory, Guangzhou 510005, China

Received:2023-11-23 Revised:2024-01-22 Online:2024-04-20 Published:2024-02-01
Contact: Hui Li, Guangming Wu E-mail:huili19@163.com;wu_guangming@gzlab.ac.cn
Supported by:
National Natural Science Foundation of China(31801181);Chongqing Natural Science Foundation General Project(cstc2020jcyj-msxmX0903);Scientific Research Project of Chongqing College of Electronic Engineering(22XJDXWT35)

Abstract

Abstract:

The tumor suppressor programmed cell death 4 (PDCD4) is downregulated in various tumor tissues indicating poor prognosis. PDCD4 is the first protein found to resist tumor transformation, invasion, and metastasis by inhibiting translation. The functions of PDCD4 dependent on its structures are affected by extracellular signals. It regulates tumor-related proteins through a variety of mechanisms, especially involved in two major signaling pathways, PI3K-Akt-mTOR and MAPK. By analyzing the relationship between the structures, functions and diseases of PDCD4, this review summarizes the roles of PDCD4 in several physiological processes and diseases such as apoptosis, autophagy, tumor, and inflammation in recent years, thereby providing insights for the study of the signaling pathways of PDCD4 and related proteins and the treatment of diseases targeting them.

Key words: PDCD4, translation inhibition, tumor, structural elements, functions

Hui Li, Guangming Wu. Progress on the relationship between tumor suppressor PDCD4 and diseases based on the analysis of structural characteristics[J]. Hereditas(Beijing), 2024, 46(4): 290-305.

Figures/Tables 4

Fig. 1

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Table 1

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结构域或序列或位点	个数	位置	功能	参考文献
MA3结构域	2	157~302 aa, 319~449 aa	与eIF4A结合，阻碍正常的蛋白翻译起始复合物形成，从而抑制帽依赖性蛋白从头翻译。其中重要的氨基酸为E249、D253、D414、D418。	[9~11,17~19]
核定位信号(NLSs)	2	58~64 aa, 448~454 aa	PDCD4在大部分正常组织中主要表达于细胞核内。	[12]
出核信号 (NESs)	2	182~192 aa, 241~251 aa	PDCD4受细胞外信号影响可出核，表达于细胞质。	[12]
RNA结合碱性氨基酸簇(RBM)	2	58~66 aa, 100~107aa	RNA结合域中与RNA结合序列，调节RNA代谢。	[7]
PABP结合簇	1	RNA结合域的后端	与PABP结合，影响与RNA结合的稳定性和核糖体的招募，起关键作用的氨基酸为K114K115和V123W124。	[31]
磷酸化位点	4	Ser67	被Akt或S6K磷酸化，进一步促进71和76位点的磷酸化。	[13,14]
		Ser71, Ser76	磷酸化后与βTRCP结合，使PDCD4泛素化后至蛋白酶体降解。	[14,30,33]
		Ser457	被Akt磷酸化，促进出核。	[13]
甲基化位点	1	Arg110	在营养缺乏期间促进肿瘤的生存能力。	[15,38]

Progress on the relationship between tumor suppressor PDCD4 and diseases based on the analysis of structural characteristics

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