Thrombospondin-1 type-1 repeat domain (TSR1)

Thrombospondin-1 (TSP-1) is a large, multifunctional matricellular glycoprotein, and its type-1 repeat (TSR) domains are central to its biological activity, particularly in regulating angiogenesis and TGF-beta activation (UniProt P35442). These TSR domains contain specific motifs, such as the CSVTCG sequence which binds to the CD36 receptor on endothelial cells, triggering a signaling cascade that leads to apoptosis and the inhibition of tube formation (PubMed: 10545156). Furthermore, the TSRs are responsible for the non-proteolytic activation of latent TGF-beta through the KRFK motif, making them significant players in fibrotic diseases and tumor progression (PubMed: 11134020). Therapeutic strategies have focused on developing TSR-mimetic peptides, such as ABT-510 and ABT-898, which were designed to harness the anti-angiogenic properties of TSP-1 for cancer treatment (ClinicalTrials.gov: NCT00046111). Despite promising preclinical results, these mimetics have faced challenges in clinical trials due to limited efficacy as monotherapies and the complex pleiotropic effects of TSP-1 signaling.

Other names

TSP-1 type 1 repeatsThrombospondin type 1 repeatTSR domainMal-like repeatsThrombospondin-1 TSR

Mimicry of endogenous anti-angiogenic activity by binding to CD36 receptors on endothelial cells and activating latent TGF-beta via the KRFK motif.