Cargando…
IU1 suppresses proliferation of cervical cancer cells through MDM2 degradation
Previous studies have demonstrated that the antitumor potential of IU1 (a pharmacological compound), which was mediated by selective inhibition of proteasome-associated deubiquitinase ubiquitin-specific protease 14 (USP14). However, the underlying molecular mechanisms remain elusive. It has been wel...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545697/ https://www.ncbi.nlm.nih.gov/pubmed/33061808 http://dx.doi.org/10.7150/ijbs.47999 |
_version_ | 1783592081929797632 |
---|---|
author | Xu, Liu Wang, Jing Yuan, Xiaoning Yang, Shuhua Xu, Xiaolong Li, Kai He, Yanqi Wei, Lei Zhang, Jingwei Tian, Yihao |
author_facet | Xu, Liu Wang, Jing Yuan, Xiaoning Yang, Shuhua Xu, Xiaolong Li, Kai He, Yanqi Wei, Lei Zhang, Jingwei Tian, Yihao |
author_sort | Xu, Liu |
collection | PubMed |
description | Previous studies have demonstrated that the antitumor potential of IU1 (a pharmacological compound), which was mediated by selective inhibition of proteasome-associated deubiquitinase ubiquitin-specific protease 14 (USP14). However, the underlying molecular mechanisms remain elusive. It has been well established that mdm2 (Murine double minute 2) gene was amplified and/or overexpressed in a variety of human neoplasms, including cervical cancer. Furthermore, MDM2 is critical to cervical cancer development and progression. Relatively studies have reported that USP15 and USP7 stabilized MDM2 protein levels by removing its ubiquitin chain. In the current study, we studied the cell proliferation status after IU1 treatment and the USP14-MDM2 protein interaction in cervical cancer cells. This study experimentally revealed that IU1 treatment reduced MDM2 protein expression in HeLa cervical cancer cells, along with the activation of autophagy-lysosomal protein degradation and promotion of ubiquitin-proteasome system (UPS) function, thereby blocked G0/G1 to S phase transition, decreased cell growth and triggered cell apoptosis. Thus, these results indicate that IU1 treatment simultaneously targets two major intracellular protein degradation systems, ubiquitin-proteasome and autophagy-lysosome systems, which leads to MDM2 degradation and contributes to the antitumor effect of IU1. |
format | Online Article Text |
id | pubmed-7545697 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-75456972020-10-13 IU1 suppresses proliferation of cervical cancer cells through MDM2 degradation Xu, Liu Wang, Jing Yuan, Xiaoning Yang, Shuhua Xu, Xiaolong Li, Kai He, Yanqi Wei, Lei Zhang, Jingwei Tian, Yihao Int J Biol Sci Research Paper Previous studies have demonstrated that the antitumor potential of IU1 (a pharmacological compound), which was mediated by selective inhibition of proteasome-associated deubiquitinase ubiquitin-specific protease 14 (USP14). However, the underlying molecular mechanisms remain elusive. It has been well established that mdm2 (Murine double minute 2) gene was amplified and/or overexpressed in a variety of human neoplasms, including cervical cancer. Furthermore, MDM2 is critical to cervical cancer development and progression. Relatively studies have reported that USP15 and USP7 stabilized MDM2 protein levels by removing its ubiquitin chain. In the current study, we studied the cell proliferation status after IU1 treatment and the USP14-MDM2 protein interaction in cervical cancer cells. This study experimentally revealed that IU1 treatment reduced MDM2 protein expression in HeLa cervical cancer cells, along with the activation of autophagy-lysosomal protein degradation and promotion of ubiquitin-proteasome system (UPS) function, thereby blocked G0/G1 to S phase transition, decreased cell growth and triggered cell apoptosis. Thus, these results indicate that IU1 treatment simultaneously targets two major intracellular protein degradation systems, ubiquitin-proteasome and autophagy-lysosome systems, which leads to MDM2 degradation and contributes to the antitumor effect of IU1. Ivyspring International Publisher 2020-09-16 /pmc/articles/PMC7545697/ /pubmed/33061808 http://dx.doi.org/10.7150/ijbs.47999 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Xu, Liu Wang, Jing Yuan, Xiaoning Yang, Shuhua Xu, Xiaolong Li, Kai He, Yanqi Wei, Lei Zhang, Jingwei Tian, Yihao IU1 suppresses proliferation of cervical cancer cells through MDM2 degradation |
title | IU1 suppresses proliferation of cervical cancer cells through MDM2 degradation |
title_full | IU1 suppresses proliferation of cervical cancer cells through MDM2 degradation |
title_fullStr | IU1 suppresses proliferation of cervical cancer cells through MDM2 degradation |
title_full_unstemmed | IU1 suppresses proliferation of cervical cancer cells through MDM2 degradation |
title_short | IU1 suppresses proliferation of cervical cancer cells through MDM2 degradation |
title_sort | iu1 suppresses proliferation of cervical cancer cells through mdm2 degradation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545697/ https://www.ncbi.nlm.nih.gov/pubmed/33061808 http://dx.doi.org/10.7150/ijbs.47999 |
work_keys_str_mv | AT xuliu iu1suppressesproliferationofcervicalcancercellsthroughmdm2degradation AT wangjing iu1suppressesproliferationofcervicalcancercellsthroughmdm2degradation AT yuanxiaoning iu1suppressesproliferationofcervicalcancercellsthroughmdm2degradation AT yangshuhua iu1suppressesproliferationofcervicalcancercellsthroughmdm2degradation AT xuxiaolong iu1suppressesproliferationofcervicalcancercellsthroughmdm2degradation AT likai iu1suppressesproliferationofcervicalcancercellsthroughmdm2degradation AT heyanqi iu1suppressesproliferationofcervicalcancercellsthroughmdm2degradation AT weilei iu1suppressesproliferationofcervicalcancercellsthroughmdm2degradation AT zhangjingwei iu1suppressesproliferationofcervicalcancercellsthroughmdm2degradation AT tianyihao iu1suppressesproliferationofcervicalcancercellsthroughmdm2degradation |