| 朱浩楠,顾雨洁,国风.STUB1/CHIP与癌症及抗肿瘤免疫的相关性研究进展[J].安徽医药,2026,30(5):849-855. |
| STUB1/CHIP与癌症及抗肿瘤免疫的相关性研究进展 |
| Progress in the study of STUB1/CHIP correlation with cancer and anti-tumor immunity |
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| DOI：10.3969/j.issn.1009-6469.2026.05.001 |
| 中文关键词: 泛素蛋白连接酶类 热休克蛋白 70羧基末端相互作用蛋白 热休克蛋白 90 抗肿瘤免疫 肿瘤治疗 |
| 英文关键词: Ubiquitin-protein ligases C-terminus of Hsp70-interacting protein Heat shock protein 90 Antitumor immunity Tumor therapy |
| 基金项目:江苏省科技厅基金资助项目( BE2023717)；江苏省卫生健康委员会基金资助项目( M2020043)；中国消化道肿瘤临床研究公益项目( P014-038)；苏州市科技局基金资助项目( SKY2022006、SLJ202011、SLT201959) |
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| 中文摘要: |
| 热休克蛋白 70羧基末端相互作用蛋白( C-terminal of Hsp70-interacting protein，CHIP)是一种属于 U-box家族的泛素连接酶和共伴侣，在维持细胞稳态中发挥关键作用。 CHIP通过调节蛋白质的折叠 -重折叠过程，将肿瘤关键蛋白转变至蛋白酶体或溶酶体降解途径。它可通过 N端四重螺旋重复序列( tetratricopeptide repeat，TPR)域与分子伴侣［如热休克蛋白 70(HSP70)和热休克蛋白 90(HSP90)相互作用，并通过 C端 U-box域促进泛素转移至底物蛋白，从而执行泛素化降解。近年来，研究发现 E3泛素连接酶( STUB1)基因( STIP1同源性和含 U-box蛋白 1)编码的 CHIP蛋白在多种恶性肿瘤中既可发挥肿瘤抑制功能，也可能在特定条件下促进肿瘤进展，被视为一种“双面间谍”。此外， STUB1/CHIP在多种免疫细胞的分化、成熟及免疫检查点通路中均具重要调控作用。现系统综述 STUB1/CHIP在癌症进展与肿瘤免疫中的生物学功能、临床意义及潜在的治疗价值，探讨其在精准医疗和免疫治疗领域的研究前景。 |
| 英文摘要: |
| C-terminus of Hsp70-interacting protein (CHIP) is a ubiquitin ligase belonging to the U-box family and a co-chaperone thatplays a crucial role in maintaining cellular homeostasis. CHIP regulates the folding and refolding processes of proteins and directs keyoncogenic proteins toward proteasomal or lysosomal degradation pathways. It interacts with molecular chaperones such as heat shockprotein 70 (HSP70), and heat shock protein 90 (HSP90) through its N-terminal tetratricopeptide repeat (TPR) domain and facilitates ubiquitin transfer to substrate proteins via its C-terminal U-box domain, thereby mediating ubiquitination and protein degradation. Re.cent studies have shown that CHIP, encoded by the STUB1 gene (STIP1 homology and U-box containing protein 1), exhibits dual func. tions in various malignancies—it can act as a tumor suppressor by degrading oncogenic proteins, but under certain conditions, it may al.so promote tumor progression, making it a "double-edged sword" in cancer biology. Additionally, STUB1/CHIP plays a significant regu.latory role in the differentiation, maturation, and immune checkpoint pathways of various immune cells. The review systematically sum.marizes the biological functions, clinical significance, and therapeutic potential of STUB1/CHIP in cancer progression and tumor immu.nity. Furthermore, it explores its research prospects in precision medicine and immunotherapy. |
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