Mechanistic Role of the Mdm2/MdmX Lid Domain in Regulating Their Interactions with p53

被引：1

作者：

Wei, Qiuyin ^{[1
]}

Li, Chenqi ^{[1
]}

Tang, Yibing ^{[1
]}

Bai, Jinping ^{[1
]}

Li, Wang ^{[1
]}

Liu, Jidong ^{[1
]}

Su, Zhengding ^{[2
,3
]}

Cheng, Xiyao ^{[1
]}

机构：

[1] Guangxi Univ, Inst Modern Fermentat Engn & Future Foods, Sch Light Ind & Food Engn, 100 Daxuedong Rd, Nanning 530004, Peoples R China

[2] Xinjiang Univ, Sch Pharmaceut Sci, Urumqi 830017, Peoples R China

[3] Xinjiang Univ, Inst Mat Med, Urumqi 830017, Peoples R China

来源：

BIOMOLECULES | 2025年 / 15卷 / 05期

基金：

中国国家自然科学基金;

关键词：

tumor suppressor protein p53; Mdm2; MdmX; Lid; SMALL-MOLECULE ANTAGONISTS; N-TERMINAL DOMAIN; MDM2; BINDING-SITE; PHOSPHORYLATION; SIMULATIONS; MUTATION; PROTEIN; POLYUBIQUITINATION; INTERROGATION; ACTIVATION;

D O I：

10.3390/biom15050642

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

p53 functions as a critical guardian of the genome, orchestrating tumor suppression pathways and ensuring the integrity of chromosomal stability. Mdm2 and MdmX, homologous proteins, serve as negative feedback regulators of p53. In approximately half of tumor cases, overexpression of Mdm2/MdmX results in the inhibition of p53 activity. Current research focuses on designing Mdm2 and MdmX inhibitors based on the structure of lidless N-terminal forms of these proteins. However, growing evidence suggests that the lid of Mdm2 and MdmX plays a key role in the selective binding of p53 and inhibitors. Therefore, targeting the lid in the screening and design of Mdm2/MdmX inhibitors may offer a novel strategy for developing anti-cancer drugs. This review examines the impact of the Mdm2/MdmX lid on ligand binding, providing valuable insights for future research and guiding new approaches to the screening and design of innovative anti-cancer therapeutics.

引用

页数：15

共 53 条

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