Background |
Transforming growth factor beta (TGF-beta) has three isoforms (TGF-beta1, TGF-beta2, and TGF-beta3) with similar functions. The cytokine is a homodimer linked by disulfide bind. Inside cells, the cytokine forms a small latent complex with latent associated peptide (LAP). This small complex binds to latent TGF-beta binding protein (LTBP) to be secreted to extra-cellular matrix. Disassociation of the latent proteins from TGF-beta results in the release of the cytokine to its receptor. The process is called activation, which can be influenced by various factors, including proteases, metalloproteases, extreme pH, mild acidic condition, reactive oxygen species and integrins. TGF-beta is an anti-proliferation factor in normal cells. It increases the synthesis of p15 and p21, which can block the cyclin: CDK complex, and causes cells to stop at G1 phase. The cytokine can induce apoptosis through both SMAD and DAXX pathways. In cancer cells, TGF-beta signaling is altered and TGF-beta no longer stops cell proliferation. |