Scholarlink

<p>HERC4 is a well-known HERC family ubiquitin ligase in several types of cancer but its role in lung cancer remains elusive. In the present study, we found that HERC4 is highly dysregulated in lung adenocarcinoma (LUAD) and promotes LUAD cell growth. Mechanically, HERC4 interacts with translation-related proteins and specifically stabilizes RPS15, a component of 40S ribosomal subunit, by promoting its deubiquitination in a manner independent of E3 ligase activity. HERC4 collaborates with USP16, a deubiquitinase that also interacts with translation-related proteins, to stabilize RPS15 by preventing its K48-linked ubiquitination. Further studies revealed that the interaction between HERC4 and USP16 is important to regulate RPS15 and to promote LUAD cell proliferation. Knockdown of HERC4 or USP16 prevents the recruitment of translation-related proteins to ribosomes, increases their nuclear retention and reduces global translational efficacy. Overexpression of RPS15 partially rescues reduced protein translation efficiency and cell survival triggered by HERC4/USP16 knockdown. Moreover, knockdown of HERC4 or USP16 upregulates p53 and downregulates p38 via RPS15 dysregulation. In conclusion, the present study reveals a novel ubiquitination modulation on ribosomal stability and protein translation. HERC4 synergizes with USP16 to deubiquitinate and stabilize RPS15, thereby potentiating global protein translation and promoting LUAD growth. The HERC4/USP16-RPS15 axis may represent a potential therapeutic target for LUAD treatment.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

HERC4 synergizes with USP16 to promote lung adenocarcinoma growth by augmenting protein translation via stabilizing RPS15

  • 期刊论文

  • 发表日期：

    2026年7月29日

查看全文
  • Qiuyun Jiang,
  • Yiyang Liu,
  • Wenshuang Sun,
  • Ziyang Liu,
  • Na Tao,
  • Yunshu Zhao,
  • Pingfei Li,
  • Yujie Ou,
  • Yuening Sun,
  • Hongbiao Huang,
  • Jia Yu,
  • Wenhua Liang,
  • Xinliang Mao

摘要

HERC4 is a well-known HERC family ubiquitin ligase in several types of cancer but its role in lung cancer remains elusive. In the present study, we found that HERC4 is highly dysregulated in lung adenocarcinoma (LUAD) and promotes LUAD cell growth. Mechanically, HERC4 interacts with translation-related proteins and specifically stabilizes RPS15, a component of 40S ribosomal subunit, by promoting its deubiquitination in a manner independent of E3 ligase activity. HERC4 collaborates with USP16, a deubiquitinase that also interacts with translation-related proteins, to stabilize RPS15 by preventing its K48-linked ubiquitination. Further studies revealed that the interaction between HERC4 and USP16 is important to regulate RPS15 and to promote LUAD cell proliferation. Knockdown of HERC4 or USP16 prevents the recruitment of translation-related proteins to ribosomes, increases their nuclear retention and reduces global translational efficacy. Overexpression of RPS15 partially rescues reduced protein translation efficiency and cell survival triggered by HERC4/USP16 knockdown. Moreover, knockdown of HERC4 or USP16 upregulates p53 and downregulates p38 via RPS15 dysregulation. In conclusion, the present study reveals a novel ubiquitination modulation on ribosomal stability and protein translation. HERC4 synergizes with USP16 to deubiquitinate and stabilize RPS15, thereby potentiating global protein translation and promoting LUAD growth. The HERC4/USP16-RPS15 axis may represent a potential therapeutic target for LUAD treatment.