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Updated: Aug 5, 2026

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09:49

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing

Published on: July 5, 2019

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

Qiuyun Jiang1, Yiyang Liu2, Wenshuang Sun1

  • 1The Key Laboratory of Advanced Interdisciplinary Studies, The First Affiliated Hospital of Guangzhou Medical University & Guangdong Provincial Key Laboratory of Protein Modification and Diseases, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China.

Oncogene
|July 29, 2026
PubMed

Insights

HERC4 and USP16 stabilize RPS15, a ribosomal protein, promoting lung adenocarcinoma growth by enhancing protein translation. This HERC4/USP16-RPS15 pathway offers a potential therapeutic target for LUAD.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Ubiquitination Pathways

Background:

  • HERC4, a ubiquitin ligase, has known roles in various cancers.
  • Its specific function in lung adenocarcinoma (LUAD) remained unclear.
  • Understanding HERC4's role is crucial for LUAD treatment strategies.

Purpose of the Study:

  • To elucidate the role and mechanism of HERC4 in lung adenocarcinoma.
  • To investigate the interaction between HERC4, USP16, and RPS15 in LUAD.
  • To explore the HERC4/USP16-RPS15 axis as a potential therapeutic target.

Main Methods:

  • Analysis of HERC4 dysregulation in LUAD tissues.
  • Co-immunoprecipitation to study protein interactions (HERC4, USP16, RPS15).
  • Western blotting to assess ubiquitination levels and protein stability.
  • RNA interference (siRNA) to knock down HERC4 and USP16.
  • Cell proliferation assays and ribosome-bound protein analysis.

Main Results:

  • HERC4 is upregulated in LUAD and promotes cell growth.
  • HERC4 stabilizes RPS15 by deubiquitination, independent of its E3 ligase activity.
  • HERC4 collaborates with USP16 to prevent RPS15 K48-linked ubiquitination.
  • Knockdown of HERC4/USP16 reduces protein translation and increases p53, decreases p38.
  • RPS15 overexpression partially rescues these effects.

Conclusions:

  • HERC4 and USP16 synergize to deubiquitinate and stabilize RPS15.
  • This axis enhances global protein translation and promotes LUAD cell proliferation.
  • The HERC4/USP16-RPS15 pathway is a promising therapeutic target for LUAD.

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