Deubiquitinase USP8 increases ID1 stability and promotes esophageal squamous cell carcinoma tumorigenesis. (28th August 2022)

• Record Type: Journal Article
• Authors: Li, Lei; Liu, Yuhao; Zhao, Yahui; Feng, Riyue; Li, Yang; Yu, Xiao; Liu, Zhihua; Wang, Luhua
• Is Part Of: Cancer letters. Volume 542(2022)
• Publication Date: 2022-08-28
• Subjects: Deubiquitination -- USP8 -- Protein stability -- TXNIP -- ID1; USP8 ubiquitin specific peptidase 8 -- ID1 inhibitor of DNA binding 1 -- TXNIP thioredoxin interacting protein -- ESCC esophageal squamous cell carcinoma -- CHX cycloheximide; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2022.215760
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: ID1 is a labile protein implicated in the development and progression of several malignant tumors, but the mechanisms regulating ID1 stability and function in human esophageal squamous cell carcinoma (ESCC) are largely unclear. In this study, we performed an immunoprecipitation assay to screen for deubiquitinases that may interact with ID1 and identified USP8 as a novel deubiquitinase for ID1. USP8 interacts with ID1, and increases the protein level and stability of ID1 by reducing its ubiquitination. Ectopic expression of USP8 promotes ESCC tumorigenesis by suppressing ID1 degradation, whereas knockdown of USP8 results in the opposite phenotypes in vitro and in vivo . Moreover, we found that TXNIP is a novel downstream target of ID1, and USP8 promotes ESCC tumorigenesis by activating the ID1-TXNIP pathway. Increased expression of USP8 and ID1 positively correlates with reduced TXNIP expression in ESCC tissues and predicts an advanced tumor stage. Overall, our data indicate that USP8 is a novel deubiquitinase for ID1 and show the importance of the USP8-ID1-TXNIP axis in promoting ESCC tumorigenesis. Highlights: USP8 is a novel deubiquitinating enzyme for ID1. USP8 promotes ESCC tumorigenesis via stabilization and deubiquitination of ID1. TXNIP is novel downstream target of the USP8-ID1 pathway.