TGFB1 - Transforming Growth Factor Beta 1 | Elisa - Clia - Antibody - Protein

Background

Transforming Growth Factor Beta 1 (TGFB1) is a multifunctional cytokine belonging to the TGF-beta superfamily, which plays a pivotal role in cellular processes such as proliferation, differentiation, apoptosis, and extracellular matrix production. TGFB1 is synthesized as a precursor protein that undergoes proteolytic cleavage to form a mature, active dimer. The mature TGFB1 is secreted as a latent complex, which requires activation to interact with its receptors on the cell surface. This activation can be mediated by various factors, including proteases, integrins, and reactive oxygen species. TGFB1 is ubiquitously expressed in various tissues and is involved in numerous physiological and pathological processes, including embryogenesis, immune regulation, wound healing, and cancer progression.

Protein Structure

TGFB1 is a homodimeric protein, with each monomer consisting of:

• Signal Peptide: Directs the nascent polypeptide to the endoplasmic reticulum for secretion.
• Propeptide (Latency-Associated Peptide, LAP): Remains non-covalently attached to the mature TGFB1, keeping it in a latent state.
• Mature Domain: The active part of TGFB1, which binds to TGF-beta receptors. This domain forms a cystine knot structure stabilized by disulfide bonds, critical for its bioactivity.

Classification and Subtypes

TGFB1 is one of three isoforms in the TGF-beta family, alongside TGFB2 and TGFB3. Each isoform has distinct but overlapping functions in various tissues and developmental stages. TGFB1 is the most widely studied isoform due to its extensive role in immunoregulation and tissue homeostasis.

Function and Biological Significance

TGFB1 functions through a well-defined signaling pathway involving:

• Receptor Binding: TGFB1 binds to a type II TGF-beta receptor (TGFBR2), which recruits and phosphorylates a type I receptor (TGFBR1). This receptor complex phosphorylates receptor-regulated SMAD proteins (R-SMADs), primarily SMAD2 and SMAD3.
• SMAD Complex Formation: Phosphorylated R-SMADs form a complex with co-SMAD (SMAD4) and translocate to the nucleus to regulate the transcription of target genes.

The biological effects of TGFB1 include:

• Immune Regulation: TGFB1 modulates immune responses, maintaining tolerance and preventing autoimmunity. It inhibits the activation and proliferation of lymphocytes and macrophages.
• Fibrosis: TGFB1 promotes the production of extracellular matrix proteins, leading to tissue fibrosis. This is significant in wound healing but can contribute to pathological fibrosis in organs like the liver, lungs, and kidneys.
• Cancer: TGFB1 has dual roles in cancer. It acts as a tumor suppressor in early stages by inhibiting cell proliferation. However, in later stages, it promotes tumor progression, invasion, and metastasis through the induction of epithelial-mesenchymal transition (EMT).

Clinical Issues

Dysregulation of TGFB1 is associated with various diseases:

• Fibrotic Diseases: Overexpression of TGFB1 is linked to fibrotic conditions such as pulmonary fibrosis, liver cirrhosis, and systemic sclerosis.
• Cancer: Elevated levels of TGFB1 correlate with poor prognosis in several cancers, including breast, prostate, and pancreatic cancer.
• Autoimmune Diseases: Altered TGFB1 signaling can contribute to the pathogenesis of autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Summary

Transforming Growth Factor Beta 1 (TGFB1) is a crucial cytokine involved in regulating cell growth, differentiation, apoptosis, and extracellular matrix production. Its signaling pathway plays a vital role in maintaining tissue homeostasis and immune regulation. Dysregulation of TGFB1 is implicated in a range of diseases, including fibrosis, cancer, and autoimmune disorders. Understanding the complex roles of TGFB1 in various biological processes is essential for developing therapeutic strategies targeting TGFB1-related pathologies.