Latency-associated peptide (LAP)

Latency-associated peptide (LAP) is the N-terminal pro-domain of the transforming growth factor-beta (TGF-β) precursor. Following synthesis, the TGF-β precursor is cleaved by the protease furin into LAP and the mature TGF-β growth factor, which remain non-covalently associated to form the Small Latent Complex (SLC) (1). This association is crucial for maintaining TGF-β in an inactive state, preventing it from interacting with its signaling receptors (2). LAP often contains an RGD motif that allows it to bind to specific integrins, such as αvβ6 and αvβ8, which facilitate the mechanical release and activation of TGF-β in response to cellular tension or environmental cues (3). In pathological conditions like cancer and fibrosis, LAP-bound TGF-β is overexpressed on the surface of regulatory T cells and myofibroblasts, contributing to an immunosuppressive microenvironment and excessive extracellular matrix deposition (4). Therapeutic agents targeting LAP, including monoclonal antibodies like SRK-181 and ABBV-151, are designed to block the activation of TGF-β1 specifically, offering a more targeted approach than global TGF-β inhibition to minimize systemic toxicities (5).

Other names

LAP-TGF-beta1TGF-beta-1 latency-associated peptidePro-TGF-beta1Latency-associated peptide of transforming growth factor beta-1

Inhibition of TGF-beta activation by stabilizing the latent complex or blocking the interaction with activating integrins.