Related Experiment Video

Updated: May 8, 2026

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
09:17

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions

Published on: August 2, 2018

Proteomic analysis of signaling network regulation in renal cell carcinomas with differential hypoxia-inducible

Lokesh Dalasanur Nagaprashantha1, Tatjana Talamantes, Jyotsana Singhal

  • 1Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, Texas, United States of America.

Plos One
|August 14, 2013
PubMed
Abstract

Insights

Von Hippel-Lindau (VHL) protein loss in renal tumors drives cancer via hypoxia-inducible factor-2α (HIF2α). This study reveals key protein and metabolic differences, including glutaminolysis reliance, offering targets for VHL-mutant cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Proteomics

Background:

  • Loss of von Hippel-Lindau (VHL) protein function causes aggressive, treatment-resistant renal tumors.
  • In VHL-mutant renal tumors, oncogenesis involves increased hypoxia-inducible factor-2α (HIF2α), unlike other cancers.

Purpose of the Study:

  • To investigate proteomic and metabolic differences in VHL-mutant renal cell carcinoma.
  • To identify potential therapeutic targets for VHL-mutant renal tumors.

Main Methods:

  • Utilized renal carcinoma cell lines with distinct VHL genotypes (mutant vs. wild-type).
  • Employed label-free liquid chromatography-mass spectrometry-based proteomics to quantify peptide intensities.
  • Performed pathway analyses on proteomic data.

Main Results:

  • Identified differential regulation of proteins crucial for cancer cell survival, proliferation, and stress resistance.
  • Observed increased expression of cellular energy pathway enzymes and mitochondrial 60-kDa heat shock protein.
  • Found significant reliance on glutaminolysis in VHL-mutant renal cell carcinoma, contrasting with typical tumor glycolysis dependence.

Conclusions:

  • Pathway analysis confirmed distinct molecular and cellular function regulation in VHL-mutant renal cell carcinoma, impacting energetics, metabolism, and proliferation.
  • The characterized proteome provides a basis for developing targeted therapies for advanced VHL-mutant, HIF2α-over-expressing renal tumors.

More Related Videos

The Use of Reverse Phase Protein Arrays (RPPA) to Explore Protein Expression Variation within Individual Renal Cell Cancers12:22

The Use of Reverse Phase Protein Arrays (RPPA) to Explore Protein Expression Variation within Individual Renal Cell Cancers

Published on: January 22, 2013

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
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...