Transcription factor EB (TFEB) is a member of the MiTF/TFE (Microphthalmia/TFE) subfamily of basic/helix-loop-helix/leucine zipper transcription factors. This group of proteins is involved in the proliferation and development of specific cell types such as osteoclasts or melanocytes. Recently scientists have begun to uncover the roles of MiTF/TFE proteins in organelle biogenesis and energy metabolism (1). TFEB, for example, is a known regulator of lysosome biogenesis. By binding to motifs known as Coordinated Lysosomal Expression and Regulation (CLEAR) elements found within the promoters of lysosomal genes TFEB is able to activate their transcription (1). These target genes include the autophagy genes UVRAG, ATG9B, MAP1LC3B, and SQSTM1. In this manner TFEB can regulate energy metabolism by influencing the levels of lysosomes and autophagosomes within the cell in response to nutrient levels (1). Under normal conditions the kinase mTORC1 phosphorylates TFEB to mediate its retention in the cytosol. Upon starvation mTORC1 is inactivated allowing TFEB to translocate to the nucleus where it can bind target gene promoters (1). TFEB is also induced during cell differentiation programs. For example, osteoclasts are cells involved in skeletal remodeling through the secretion of lysosomal hydrolases. TFEB expression is required to support the increased demand for lysosomal biogenesis in osteoclasts (1).
In a recent study of HIF1-alpha regulation, the Semenza group at Johns Hopkins demonstrated HIF1-alpha is degraded through chaperone-mediated autophagy (2). Using the TFEB antibody to measure protein levels by western blot the authors showed increased TFEB levels enhance autophagy and the degradation of HIF1-alpha. Kuiper et al. used the TFEB antibody to characterize TFEB expression in renal cell carcinomas (3). This particular cell line contains a translocation that fuses the TFEB gene region with the regulatory region of the Alpha gene (3). Through western blotting with the TFEB antibody and RT-PCR the authors of this study showed increased expression of Alpha-TFEB compared to wildtype (3). Additionally immunofluorescence with the TFEB antibody showed predominant nuclear localization, indicating TFEB is likely active in these cells (3). In an attempt to shed light on the role of TFEB in renal cell carcinoma, Huan et al. examined its normal functions in cell culture systems (4). By overexpressing TFEB and monitoring levels by western blotting with the TFEB antibody they identified E-cadherin as an upregulated target (4). Then through chromatin immunoprecipitation with TFEB antibody this upregulation was shown to be through direct binding to the E-cadherin promoter (4).
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