Transforming growth factor beta 1 latent complex with latency-associated peptide (Latent TGF-beta 1)

Transforming growth factor beta 1 (TGF-β1) is synthesized as a precursor protein that is cleaved into a mature cytokine and a pro-domain called the latency-associated peptide (LAP). These two components remain non-covalently associated to form the Small Latent Complex (SLC), which prevents TGF-β1 from binding to its receptors (UniProt P01137). The latent complex is often further linked to proteins like GARP on the surface of regulatory T cells or LTBPs in the extracellular matrix, creating a reservoir of inactive cytokine (PubMed: 30104371). Activation of TGF-β1 requires the physical release of the mature dimer from LAP, a process often mediated by integrins like αvβ6 and αvβ8 in response to mechanical stress or specific proteases (PubMed: 28848666). In the context of cancer, the release of active TGF-β1 from the latent complex contributes to a highly immunosuppressive tumor microenvironment, facilitating immune evasion and resistance to checkpoint inhibitors (Scholar Rock, 2024). In fibrotic diseases, excessive activation of the latent complex drives the differentiation of fibroblasts into myofibroblasts and the accumulation of collagen (PubMed: 32661138). Therapeutic agents such as SRK-181 and ABBV-151 are designed to selectively bind the latent TGF-β1 complex and prevent its activation, rather than neutralizing the active cytokine systemically. This selective approach aims to maximize therapeutic efficacy in diseased tissues while minimizing the severe cardiovascular and cutaneous toxicities associated with global TGF-β inhibition (AbbVie, 2023).

Other names

TGF-beta 1/LAP complexSmall Latent ComplexSLCpro-TGF-beta 1Latent TGFB1

Selective inhibition of the activation of TGF-beta 1 from its latent complex, preventing the release of the active growth factor.