Related Experiment Video

Updated: Apr 8, 2026

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
09:40

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

3.3K

DDB2 modulates TGF-β signal transduction in human ovarian cancer cells by downregulating NEDD4L

Ran Zhao1, Tiantian Cui1, Chunhua Han1

  • 1Division of Radiobiology, Department of Radiology, The Ohio State University Medical Center, Columbus, OH 43210, USA.

Nucleic Acids Research
|July 2, 2015
PubMed

Insights

DNA damage-binding protein 2 (DDB2) regulates ovarian cancer growth by controlling the NEDD4L gene and transforming growth factor-beta (TGF-β) signaling. This DDB2-NEDD4L interaction fine-tunes TGF-β pathways, impacting tumor progression.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • DNA damage-binding protein 2 (DDB2) expression correlates with ovarian cancer prognosis.
  • DDB2's role in transcriptional regulation suggests a link to treatment outcomes.
  • The precise molecular mechanisms underlying DDB2's function in ovarian cancer require elucidation.

Purpose of the Study:

  • To identify downstream genes regulated by DDB2 in ovarian cancer.
  • To elucidate the mechanism by which DDB2 regulates its target genes.
  • To investigate the impact of DDB2 on transforming growth factor-beta (TGF-β) signaling in ovarian cancer cells.

Main Methods:

  • Gene microarray analysis to identify DDB2-regulated genes.
  • Chromatin immunoprecipitation (ChIP) assays to confirm DDB2 binding to the NEDD4L promoter.
  • Western blotting and quantitative PCR to assess protein and gene expression levels.
  • Functional assays to evaluate TGF-β signaling pathway activation and cellular response.

Main Results:

  • Neural precursor cell expressed, developmentally downregulated 4-Like (NEDD4L) was identified as a novel downstream target of DDB2.
  • DDB2 directly binds to the NEDD4L promoter and recruits enhancer of zeste homolog 2 (EZH2) to repress NEDD4L transcription via H3K27me3.
  • DDB2 enhances TGF-β signaling and increases ovarian cancer cell sensitivity to TGF-β-induced growth inhibition.

Conclusions:

  • DDB2 represses NEDD4L transcription through epigenetic modification at the NEDD4L promoter.
  • DDB2 promotes TGF-β signaling by downregulating NEDD4L, a negative regulator of this pathway.
  • The DDB2-NEDD4L interaction represents a novel regulatory mechanism influencing TGF-β signaling and tumor growth in ovarian cancer.

More Related Videos

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

7.3K
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

14.8K

Related Concept Videos

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...
11.0K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
3.0K
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...
5.1K