STAMBPL1,也称为STAM结合蛋白样1,是一种重要的去泛素化酶,特异性地切割Lys-63连接的泛素链。去泛素化是一种重要的蛋白质翻译后修饰过程,参与调控蛋白质的稳定性、活性和功能,影响多种生物学过程,包括细胞周期、信号传导、转录调控和蛋白质降解。
STAMBPL1在多种癌症中发挥重要作用,包括胃癌、结直肠癌、肝癌、肾细胞癌、肺腺癌和前列腺癌。在胃癌中,STAMBPL1的表达与肿瘤的进展和不良预后相关。敲低STAMBPL1可以抑制胃癌细胞的增殖、侵袭和迁移,并促进凋亡[5]。在结直肠癌中,STAMBPL1的表达也显著升高,并且与肿瘤的进展和不良预后相关。敲低STAMBPL1可以抑制结直肠癌细胞系的生长、侵袭和迁移,并促进凋亡[4]。在肝癌中,STAMBPL1通过调节EGFR的稳定性和转录后修饰,促进肝癌的发生和发展[1]。在肾细胞癌中,STAMBPL1通过调节AXL的稳定性,影响肿瘤的间质表型和免疫逃逸[2]。在肺腺癌中,STAMBPL1通过抑制DHRS2的表达,促进肺腺癌的发生和发展[3]。在前列腺癌中,STAMBPL1通过抑制XIAP的降解,抑制细胞凋亡[7]。
STAMBPL1的调控机制包括转录调控、翻译后修饰和蛋白质相互作用。在肝癌中,SREBP1可以转录调控STAMBPL1的表达,并通过Wnt/β-catenin信号通路促进肝癌的发生和发展[6]。在胃癌和结直肠癌中,NF-κB信号通路可以调节STAMBPL1的表达,并影响肿瘤的发生和发展[4,5]。此外,STAMBPL1还可以与其他蛋白质相互作用,影响其功能和活性。
STAMBPL1的研究有助于深入理解去泛素化酶的生物学功能和疾病发生机制,为癌症的治疗和预防提供新的思路和策略。STAMBPL1可能成为一种新的癌症治疗靶点,通过抑制其表达或活性,抑制肿瘤的发生和发展。此外,STAMBPL1还可以作为一种新的癌症诊断和预后标志物,用于预测患者的预后和治疗效果。
参考文献:
1. Zhang, Hongli, Wang, Zixuan, Zhang, Jian, Chen, Wei-Dong, Wang, Yan-Dong. 2024. A MYC-STAMBPL1-TOE1 positive feedback loop mediates EGFR stability in hepatocellular carcinoma. In Cell reports, 43, 114812. doi:10.1016/j.celrep.2024.114812. https://pubmed.ncbi.nlm.nih.gov/39388352/
2. Huang, Shiyu, Qin, Xuke, Fu, Shujie, Chen, Zhiyuan, Wang, Lei. 2024. STAMBPL1/TRIM21 Balances AXL Stability Impacting Mesenchymal Phenotype and Immune Response in KIRC. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12, e2405083. doi:10.1002/advs.202405083. https://pubmed.ncbi.nlm.nih.gov/39527690/
3. Yang, Xiang, Ling, Liqun, Li, Changhong, Wang, Yumin, Hu, Lijuan. 2023. STAMBPL1 promotes the progression of lung adenocarcinoma by inhibiting DHRS2 expression. In Translational oncology, 35, 101728. doi:10.1016/j.tranon.2023.101728. https://pubmed.ncbi.nlm.nih.gov/37393834/
4. Zhou, Xinghua, Cheng, Yue, Kang, Jian, Mao, Gang. . STAM-binding Protein-like 1 Promotes Growth and Migration of Colorectal Cancer by NF-κB Pathway. In Protein and peptide letters, 30, 1058-1066. doi:10.2174/0109298665272785231103104118. https://pubmed.ncbi.nlm.nih.gov/38008943/
5. Yu, Da-Jun, Qian, Jun, Jin, Xin, Guo, Chen-Xu, Yue, Xi-Cheng. 2019. STAMBPL1 knockdown has antitumour effects on gastric cancer biological activities. In Oncology letters, 18, 4421-4428. doi:10.3892/ol.2019.10789. https://pubmed.ncbi.nlm.nih.gov/31611951/
6. Jin, Junyi, Wang, Yihui, Hu, Yaoyuan. 2024. STAMBPL1, transcriptionally regulated by SREBP1, promotes malignant behaviors of hepatocellular carcinoma cells via Wnt/β-catenin signaling pathway. In Molecular carcinogenesis, 63, 2158-2173. doi:10.1002/mc.23801. https://pubmed.ncbi.nlm.nih.gov/39150093/
7. Chen, Xi, Shi, Hongzhe, Bi, Xingang, Li, Yajian, Huang, Zhenhua. 2019. Targeting the deubiquitinase STAMBPL1 triggers apoptosis in prostate cancer cells by promoting XIAP degradation. In Cancer letters, 456, 49-58. doi:10.1016/j.canlet.2019.04.020. https://pubmed.ncbi.nlm.nih.gov/31004702/