Abstract
Hypoxia/anoxia promotes tumor aggressiveness and negatively impacts tumor response to therapy. Coordinate regulation of HIF-dependent and HIF-independent pathways has been shown to contribute to cellular adaptation to hypoxic stress, and to couple macromolecular synthesis rates to reduced energy availability. An important component of this type of adaptation is the activation of the endoplasmic reticulum kinase PERK by acute or prolonged hypoxia. Activated PERK subsequently induces phosphorylation of the translation initiation factor eIF2α and translational upregulation of the transcription factor ATF4. ATF4 is a basic leucine-zipper (bZip) transcription factor, which regulates amino acid metabolism, cellular redox state, and antistress responses. ATF4 expression can be regulated at transcriptional, translational, and post-translational levels. The functional activation of ATF4 under hypoxia and the overexpression of ATF4 in hypoxic areas of clinical samples of human tumors suggest that ATF4 plays a role in tumor hypoxic adaptation. Here we summarize recent findings regarding the regulation of ATF4 in transformed cells, clinical tumor samples and tumor models, and speculate on its potential role in tumor progression and chemoresistance.
Current Molecular Medicine
Title: ATF4, an ER Stress and Hypoxia-Inducible Transcription Factor and its Potential Role in Hypoxia Tolerance and Tumorigenesis
Volume: 9 Issue: 4
Author(s): Jiangbin Ye and Constantinos Koumenis
Affiliation:
Keywords: ATF4, hypoxia, ER stress
Abstract: Hypoxia/anoxia promotes tumor aggressiveness and negatively impacts tumor response to therapy. Coordinate regulation of HIF-dependent and HIF-independent pathways has been shown to contribute to cellular adaptation to hypoxic stress, and to couple macromolecular synthesis rates to reduced energy availability. An important component of this type of adaptation is the activation of the endoplasmic reticulum kinase PERK by acute or prolonged hypoxia. Activated PERK subsequently induces phosphorylation of the translation initiation factor eIF2α and translational upregulation of the transcription factor ATF4. ATF4 is a basic leucine-zipper (bZip) transcription factor, which regulates amino acid metabolism, cellular redox state, and antistress responses. ATF4 expression can be regulated at transcriptional, translational, and post-translational levels. The functional activation of ATF4 under hypoxia and the overexpression of ATF4 in hypoxic areas of clinical samples of human tumors suggest that ATF4 plays a role in tumor hypoxic adaptation. Here we summarize recent findings regarding the regulation of ATF4 in transformed cells, clinical tumor samples and tumor models, and speculate on its potential role in tumor progression and chemoresistance.
Export Options
About this article
Cite this article as:
Ye Jiangbin and Koumenis Constantinos, ATF4, an ER Stress and Hypoxia-Inducible Transcription Factor and its Potential Role in Hypoxia Tolerance and Tumorigenesis, Current Molecular Medicine 2009; 9 (4) . https://dx.doi.org/10.2174/156652409788167096
DOI https://dx.doi.org/10.2174/156652409788167096 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Na+-H+ Exchanger, pH Regulation and Cancer
Recent Patents on Anti-Cancer Drug Discovery 3-Substituted Isocoumarins as Thymidine Phosphorylase Inhibitors
Letters in Drug Design & Discovery Bio-Activities and Syntheses Developments of Triptolides
Mini-Reviews in Organic Chemistry Anticancer Potential and Molecular Targets of Pristimerin: A Mini- Review
Current Cancer Drug Targets Edible Transgenic Plant Vaccines for Different Diseases
Current Pharmaceutical Biotechnology Ectopic Thyroid Gland: Description of a Case and Review of the Literature
Endocrine, Metabolic & Immune Disorders - Drug Targets A Review on the Expression and Metabolic Features of Orphan Human Cytochrome P450 2S1 (CYP2S1)
Current Drug Metabolism Testicular Germ Cell Tumors: A Paradigm for the Successful Treatment of Solid Tumor Stem Cells
Current Cancer Therapy Reviews Cyclooxygenase-2: Potential Role in Regulation of Drug Efflux and Multidrug Resistance Phenotype
Current Pharmaceutical Design Tailored Angiogenesis Inhibition in Cancer Therapy: Respecting the Heart to Improve the Net Outcome
Current Signal Transduction Therapy P2Y Receptors: Focus on Structural, Pharmacological and Functional Aspects in the Brain
Current Medicinal Chemistry RNA Interference: A New Targeted Tumour Therapy?
Current Cancer Therapy Reviews Targeting the Akt Kinase to Modulate Survival, Invasiveness and Drug Resistance of Cancer Cells
Current Medicinal Chemistry Defensive and Offensive Cross-Reactive Antibodies Elicited by Pathogens: The Good, the Bad and the Ugly
Current Medicinal Chemistry Enhanced Gene Delivery and/or Efficacy by Functional Peptide and Protein
Current Topics in Medicinal Chemistry The Endothelin Axis: A Novel Target for Pharmacotherapy of Female Malignancies
Current Vascular Pharmacology The Application of Natural Products in Cancer Therapy by Targeting Apoptosis Pathways
Current Drug Metabolism Cervical Squamous Intraepithelial Lesions Among HIV-Positive Women on Antiretroviral Therapy in Kenya
Current HIV Research MicroRNAs: Regulators of TLR2-Mediated Probiotic Immune Responses
MicroRNA Novel Derivatives of Benfluron and Dimefluron Synthesis and Anticancer activity
Letters in Drug Design & Discovery