Regulation and Signaling of TGF-β Autoinduction

Cell signaling is a vital part of biological life. it helps coordinating various cellular processes including cellsurvival, cell growth, cell death, and cell interaction with the microenvironment and other cells. in general, cellsignaling 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 istransforming growth factor-beta (tgf-β). tgf-β signaling is mainly mediated by suppressor of mothers againstdecapentaplegic (smad) proteins, but it also interacts with other pathways such as the ras and mitogen-activatedprotein kinase (mapk) signaling pathways. furthermore, tgf-β can have a dual role depending on the cellularand microenvironmental context, in which it can act as either a growth promoter or a growth inhibitor. it hasbeen known that tgf-β can self-induce its ligand production, thereby prolonging and amplifying its effect oncells and their microenvironment. the aim of this review is to discuss the regulation and signaling of tgf-βautoinduction, which still remain to be elucidated. several factors have been found to facilitate tgf-βautoinduction, which include the activator protein-1 (ap1) complex, smad3-dependent signaling, and non-smadsignaling pathways. on the other hand, the lim (lin11, isl-1 and mec-3) domain only 7 (lmo7) protein cansuppress tgf-β autoinduction by interfering with the activities of ap-1 and smad3. since tgf-β autoinductionis implicated in various pathological conditions, better understanding of its regulation and signaling can providenew directions for therapy.