Transforming growth factor beta

Transforming Growth Factor Beta

Computer graphic of TGF-beta

Transforming Growth Factor Beta (TGF-_) is a multifunctional peptide that controls proliferation, cellular differentiation, and other functions in most cells. It belongs to the transforming growth factor beta superfamily of cytokines.

Structure

TGF-_ is a secreted protein that exists in three isoforms in mammals: TGF-_1, TGF-_2, and TGF-_3. These isoforms are encoded by separate genes and are highly conserved across species. The active form of TGF-_ is a dimeric protein that is stabilized by a disulfide bond.

Function

TGF-_ plays a crucial role in cellular processes such as cell growth, apoptosis, and cellular differentiation. It is involved in the regulation of the immune system, wound healing, and embryonic development. TGF-_ signaling is initiated when the ligand binds to a type II receptor, which then recruits and phosphorylates a type I receptor. This receptor complex then phosphorylates receptor-regulated SMADs (R-SMADs), which translocate to the nucleus to regulate gene expression.

Diagram of SMAD-mediated apoptosis

Signaling Pathway

The TGF-_ signaling pathway involves several key components, including the TGF-_ receptors, SMAD proteins, and various co-factors. Upon ligand binding, the type II receptor phosphorylates the type I receptor, which in turn phosphorylates R-SMADs. These R-SMADs form a complex with co-SMADs and translocate to the nucleus to regulate target gene expression.

Role in Disease

TGF-_ is implicated in various diseases, including cancer, fibrosis, and autoimmune disorders. In cancer, TGF-_ can act as both a tumor suppressor and a tumor promoter, depending on the context. It is known to inhibit the early stages of tumor development but can promote tumor progression and metastasis in later stages.

Therapeutic Applications

Due to its involvement in numerous pathological conditions, TGF-_ is a target for therapeutic intervention. Strategies include the use of TGF-_ inhibitors, receptor blockers, and antisense oligonucleotides to modulate its activity in diseases such as cancer and fibrosis.

Diagram of the DAXX pathway related to TGF-_ signaling

Related Pages

• Cytokine
• SMAD protein
• Cell signaling
• Growth factor

References

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  Transforming growth factor beta

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  SMAD apoptosis pathway

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  DAXX Pathway