Related Experiment Video

Updated: May 29, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

6.7K

USP5 stabilizes YTHDF1 to control cancer immune surveillance through mTORC1-mediated phosphorylation

Na Shao1, Lei Xi2, Yangfan Lv3

  • 1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), The Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China.

Nature Communications
|February 3, 2025
PubMed

Insights

The study reveals USP5 stabilizes YTHDF1 protein, crucial for cancer growth and immune evasion. Inhibiting USP5 alongside PD-L1 therapy enhances anti-tumor immunity, offering a new cancer treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • YTHDF1 protein promotes tumor growth and resistance to immune checkpoint blockade.
  • Understanding YTHDF1 protein stability is key to improving cancer treatments.

Purpose of the Study:

  • To elucidate the molecular mechanisms regulating YTHDF1 protein stability.
  • To explore the therapeutic potential of targeting YTHDF1 regulation in cancer.

Main Methods:

  • Investigated the interaction between USP5 and YTHDF1.
  • Analyzed ubiquitination and degradation pathways of YTHDF1.
  • Assessed the impact of USP5 and YTHDF1 deficiency on immune evasion.
  • Evaluated the efficacy of combining USP5 inhibition with anti-PD-L1 therapy in preclinical models.

Main Results:

  • USP5 deubiquitinates and stabilizes YTHDF1.
  • Insulin/mTORC1 signaling pathway regulates USP5 activity and YTHDF1 stability.
  • CUL7-FBXW8 E3 ligase promotes YTHDF1 degradation.
  • YTHDF1 or USP5 deficiency enhances PD-L1 expression and immune evasion.
  • Combined USP5 inhibition and anti-PD-L1 therapy boosts anti-tumor immunity.

Conclusions:

  • USP5 is a key regulator of YTHDF1 stability through deubiquitination.
  • USP5 inhibition combined with PD-(L)1 blockade represents a promising strategy for cancer therapy.
  • USP5 may serve as a predictive biomarker for patient stratification in immunotherapy.

More Related Videos

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

14.9K
Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs10:32

Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs

Published on: December 19, 2019

10.8K

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.7K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.4K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.4K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.6K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.0K