Related Experiment Video

Updated: Dec 11, 2025

Exploring the Arginine Methylome by Nuclear Magnetic Resonance Spectroscopy
07:02

Exploring the Arginine Methylome by Nuclear Magnetic Resonance Spectroscopy

Published on: December 16, 2021

1.7K

Systems level profiling of arginine starvation reveals MYC and ERK adaptive metabolic reprogramming

Caitlyn B Brashears1, Meltem Barlin1, William R Ehrhardt1

  • 1Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO, 63110, USA.

Cell Death & Disease
|August 21, 2020
PubMed

Insights

Arginine starvation therapy resistance in cancer cells involves adaptive ERK signaling and Myc-Max network activation. This study reveals metabolic shifts enhancing oxaloacetate production and glutaminolysis, crucial for understanding treatment response.

Area of Science:

  • Metabolic pathways
  • Cancer biology
  • Proteomics

Background:

  • Arginine auxotrophy, caused by argininosuccinate synthetase 1 (ASS1) silencing, is common in carcinomas and sarcomas.
  • Arginine deiminase (ADI-PEG20) therapy targets this by depleting extracellular arginine, inducing starvation.
  • Resistance to ADI-PEG20 emerges through metabolic adaptation, including ASS1 re-expression.

Purpose of the Study:

  • To understand the systemic changes induced by arginine starvation in cancer cells.
  • To characterize the adaptive mechanisms of ADI-PEG20-resistant sarcoma cells.
  • To explore multi-omic approaches for evaluating metabolically targeted therapies.

Main Methods:

  • Activity-based proteomic profiling (ABPP) before and after ADI-PEG20 treatment.
  • Phosphoproteomic profiling in sensitive and resistant sarcoma cells.
  • Integration of proteomic data with metabolomic profiling.

Main Results:

  • Arginine starvation response is mediated by adaptive ERK signaling and Myc-Max transcriptional network activation.
  • Proteomic changes facilitate oxaloacetate production via enhanced glutamine and pyruvate anaplerosis.
  • Altered lipid metabolism recycles citrate for oxidative glutaminolysis.

Conclusions:

  • Multi-omic analysis provides a systems-level understanding of cellular response to arginine starvation.
  • Adaptive signaling and metabolic reprogramming are key to resistance mechanisms.
  • These integrated approaches can evaluate responses to arginine-targeted cancer therapies.

More Related Videos

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method08:04

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method

Published on: October 23, 2018

19.6K
A Tandem Liquid Chromatography–Mass Spectrometry-based Approach for Metabolite Analysis of Staphylococcus aureus08:03

A Tandem Liquid Chromatography–Mass Spectrometry-based Approach for Metabolite Analysis of Staphylococcus aureus

Published on: March 28, 2017

10.5K

Related Concept Videos

Stringent Response in E. coli01:23

Stringent Response in E. coli

Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
199
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...
4.5K
Global Regulatory Systems01:28

Global Regulatory Systems

Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
413
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...
5.0K