TY - JOUR T1 - Regulation and Signaling of TGF-β Autoinduction TT - JF - ijmcmed JO - ijmcmed VL - 10 IS - 4 UR - http://ijmcmed.org/article-1-1787-en.html Y1 - 2021 SP - 234 EP - 247 KW - Cell signaling KW - TGF-β KW - TGF-β receptors KW - autoinduction KW - signaling pathways KW - Smad-dependent signaling KW - non-Smad-dependent signaling N2 - Cell signaling is a vital part of biological life. It helps coordinating various cellular processes including cell survival, cell growth, cell death, and cell interaction with the microenvironment and other cells. In general, cell signaling involves the attachment of signaling molecules known as ligands to specific receptors on cell surface, which then activate downstream events that dictate the cell’s response. One of the most studied ligands is transforming growth factor-beta (TGF-β). TGF-β signaling is mainly mediated by suppressor of mothers against decapentaplegic (Smad) proteins, but it also interacts with other pathways such as the Ras and mitogen-activated protein kinase (MAPK) signaling pathways. Furthermore, TGF-β can have a dual role depending on the cellular and microenvironmental context, in which it can act as either a growth promoter or a growth inhibitor. It has been known that TGF-β can self-induce its ligand production, thereby prolonging and amplifying its effect on cells and their microenvironment. The aim of this review is to discuss the regulation and signaling of TGF-β autoinduction, which still remain to be elucidated. Several factors have been found to facilitate TGF-β autoinduction, which include the activator protein-1 (AP1) complex, Smad3-dependent signaling, and non-Smad signaling pathways. On the other hand, the LIM (Lin11, Isl-1 and Mec-3) domain only 7 (LMO7) protein can suppress TGF-β autoinduction by interfering with the activities of AP-1 and Smad3. Since TGF-β autoinduction is implicated in various pathological conditions, better understanding of its regulation and signaling can provide new directions for therapy. M3 10.22088/IJMCM.BUMS.10.4.234 ER -