ETS2 Human
Description
Introduction to ETS2
ETS2 is a transcription factor encoded by the ETS2 gene in humans, belonging to the ETS family of proteins that regulate gene expression by binding to specific DNA sequences. It plays critical roles in embryonic development, tissue homeostasis, and inflammatory responses. Structural studies reveal its ETS domain facilitates DNA binding, while regulatory regions enable dynamic gene expression control. Below is a detailed analysis of its molecular mechanisms, clinical significance, and research findings.
Gene Organization
The ETS2 gene lacks canonical TATA and CAAT boxes in its promoter but contains GC-rich regions, AP2-binding sites, and Sp1 elements, enabling alternative transcriptional regulation . A long polypyrimidine tract (~250 bp) and dyad symmetry in the promoter suggest a unique regulatory mechanism distinct from TATA-dependent genes .
Protein Structure
The ETS2 protein comprises:
-
ETS Domain: A helix-turn-helix motif critical for binding ETS-specific DNA sequences (5'-CGAG-3') .
-
Autoinhibitory Module: Regulates DNA binding allosterically, though less pronounced compared to ETS1 .
-
Cooperative Binding Capability: Binds DNA motifs separated by 4–6 base pairs, enabling interactions with other transcription factors .
Cardiopoiesis and Cellular Reprogramming
ETS2 is essential for cardiac progenitor cell development:
-
Embryonic Stem Cells: ETS2 deficiency inhibits Mesp1, Nkx2.5, and Tbx5 expression, blocking cardiomyocyte differentiation .
-
Fibroblast Reprogramming: Coexpression with MESP1 or TAT-fused protein treatment converts human dermal fibroblasts into cardiac progenitors (9% efficiency), marked by KDR+/PECAM1+ markers and sarcomeric protein expression .
Inflammatory Macrophage Regulation
ETS2 drives pro-inflammatory responses in macrophages:
-
Cytokine Production: CRISPR depletion reduces IL-6, IL-8, IL-1β, and ROS generation .
-
Disease Link: A chr21q22 haplotype amplifying ETS2 expression is linked to inflammatory bowel disease, ankylosing spondylitis, and Takayasu’s arteritis .
Oncogenic and Tumor-Suppressive Roles
Autoimmune and Inflammatory Disorders
-
Disease Association: Linked to chr21q22 haplotype driving ETS2 overexpression, implicated in:
Protein Interactions
ETS2 interacts with transcription factors and regulators to modulate cellular processes:
| Partner | Function | Reference |
|---|---|---|
| C-jun | Enhances oncogenic signaling | |
| ERG | Cooperates in DNA binding and transcription | |
| Cyclin-dependent kinase 10 | Regulates cell cycle progression |
Signaling Pathways
-
Activin/Nodal: ETS2 activates this pathway while inhibiting BMP-SMAD signaling, promoting mesoderm differentiation .
-
HGF/MET: ETS2 knockdown upregulates MET phosphorylation, accelerating invasion in lung cancer .
Drug Targets
-
Inflammatory Diseases: Small molecules targeting ETS2-mediated pathways (e.g., TNF, IL-23) show anti-inflammatory potential in vitro .
-
Cancer Therapy: Dual approaches targeting ETS2 upregulation (ESCC) or downregulation (lung adenocarcinoma) may improve treatment specificity .
Diagnostic Biomarkers
Product Specs
Product Science Overview
The V-Ets Avian Erythroblastosis Virus E26 Oncogene 2, commonly referred to as ETS2, is a member of the ETS (E-twenty-six) family of transcription factors. These transcription factors are known for their role in regulating gene expression, particularly in processes related to cell development, differentiation, and proliferation. ETS2, like other ETS family members, contains a conserved ETS DNA-binding domain that allows it to bind to specific DNA sequences and regulate the transcription of target genes.
The ETS family of transcription factors was first identified in the context of avian erythroblastosis virus, where the E26 oncogene was found to be responsible for the transformation of erythroblasts into cancerous cells. The discovery of ETS2 and its homologs has since expanded our understanding of the role of these transcription factors in both normal cellular processes and oncogenesis.
ETS2 is a protein-coding gene that encodes a transcription factor involved in various cellular processes. The protein contains several functional domains, including:
- ETS DNA-binding domain: This domain is responsible for binding to specific DNA sequences and regulating the transcription of target genes.
- Pointed domain: This domain is involved in protein-protein interactions and is essential for the formation of transcriptional complexes.
ETS2 regulates the expression of numerous genes involved in cell cycle control, apoptosis, and differentiation. It plays a critical role in stem cell development, cellular senescence, and tumorigenesis .
ETS2 has been implicated in various diseases, including cancer. Overexpression or dysregulation of ETS2 can lead to aberrant cell proliferation and tumorigenesis. For example, increased expression of ETS2 has been associated with certain types of leukemia and solid tumors . Additionally, ETS2 has been linked to other conditions such as nut allergy and choriocarcinoma .
Research on ETS2 continues to uncover its role in various biological processes and diseases. Understanding the mechanisms by which ETS2 regulates gene expression and contributes to disease progression is crucial for developing targeted therapies. Inhibitors of ETS2 and its downstream signaling pathways are being explored as potential therapeutic agents for cancer and other diseases.
