TFEB/TFE3 Signaling Antibody Sampler Kit #89254

Transcription factor EB (TFEB) and transcription factor E3 (TFE3) are members of the MITF/TFE basic helix-loop-helix leucine-zipper family of transcription factors that drives the expression of a network of genes known as the Coordinated Lysosomal Expression and Regulation (CLEAR) network (1,2). These transcription factors have emerged as master regulators of the autophagy-lysosomal degradation pathway (3). In some cell types, TFEB and TFE3 appear partially redundant in terms of their ability to induce lysosomal biogenesis and regulate autophagy. However, some functions may be unique as the expression of these transcription factors is differentially regulated. The activation of TFEB and TFE3 by nutrient levels appears to be partly conserved. During normal growth conditions, TFEB is phosphorylated at Ser211 in an mTORC1-dependent manner. Phosphorylation promotes association of TFEB with 14-3-3 family proteins and retention in the cytosol. Inhibition of mTORC1 results in a loss of TFEB phosphorylation, dissociation of the TFEB/14-3-3 complex, and rapid transport of TFEB to the nucleus where it increases transcription of CLEAR and autophagy genes (4). Subsequent studies have identified additional mechanisms of TFEB regulation, including phosphorylation of Ser122, which may also occur through an mTORC1-dependent process (5). Likewise, TFE3 phosphorylation at Ser321 by mTORC1 leads to cytoplasmic retention analogous to Ser211 on TFEB (6). The collective monitoring of the activation states of these transcription factors, including their phosphorylation states, has emerged to be valuable in studies of treatment of several diseases, including cancer, neurodegeneration, metabolic disease, lysosomal storage diseases, and inflammatory diseases (7).