PDF(Pubmed)
Abstract：
Neddylation, akin to ubiquitination, represents a post‑translational modification of proteins wherein neural precursor cell‑expressed developmentally downregulated protein 8 (NEDD8) is modified on the substrate protein through a series of reactions. Neddylation plays a pivotal role in the growth and proliferation of animal cells. In colorectal cancer (CRC), it predominantly contributes to the proliferation, metastasis and survival of tumor cells, decreasing overall patient survival. The strategic manipulation of the NEDD8‑mediated neddylation pathway holds immense therapeutic promise in terms of the potential to modulate the growth of tumors by regulating diverse biological responses within cancer cells, such as DNA damage response and apoptosis, among others. MLN4924 is an inhibitor of NEDD8, and its combined use with platinum drugs and irinotecan, as well as cycle inhibitors and NEDD activating enzyme inhibitors screened by drug repurposing, has been found to exert promising antitumor effects. The present review summarizes the recent progress made in the understanding of the role of NEDD8 in the advancement of CRC, suggesting that NEDD8 is a promising anti‑CRC target.
摘要：
Neddylation，类似于泛素化，代表蛋白质的翻译后修饰，其中神经前体细胞表达的发育下调蛋白8（NEDD8）通过一系列反应在底物蛋白上进行修饰。Neddylation在动物细胞的生长和增殖中起着关键作用。在结直肠癌（CRC）中，它主要有助于扩散，肿瘤细胞的转移和存活，降低患者总体生存率。NEDD8介导的Neddylation通路的战略操纵在通过调节癌细胞内多种生物反应来调节肿瘤生长的潜力方面具有巨大的治疗前景。如DNA损伤反应和细胞凋亡，在其他人中。MLN4924是NEDD8的抑制剂，它与铂类药物和伊立替康联合使用，以及通过药物再利用筛选的循环抑制剂和NEDD激活酶抑制剂，已发现发挥有希望的抗肿瘤作用。本综述总结了在理解NEDD8在促进CRC方面的作用方面取得的最新进展，表明NEDD8是一个有前途的抗CRC目标。
