TFE3
TFE3 (transcription factor binding to IGHM enhancer 3, also known as TFEA and bHLHe33) is a basic helix-loop-helix transcription factor of the MiT/TFE family. It acts as a master regulator of lysosomal biogenesis and immune response. Browse Assay Genie's current range of TFE3 research reagents below, or read on for the biology behind the target.
TFE3 binds E-box sequences (5'-CANNTG-3'), and efficient DNA binding requires dimerisation with itself or with another MiT/TFE family member such as TFEB or MITF. It recognises the CLEAR-box sequence (5'-GTCACGTGAC-3') in the regulatory regions of many lysosomal genes and activates their expression, giving it a central role in lysosomal gene programmes. It also recognises the MUE3 box, a subset of E-boxes found in the immunoglobulin enhancer, and binds a USF/MLTF site very well.
TFE3 responds to amino acid availability downstream of MTOR. When nutrients are present, MTOR phosphorylates TFE3 and promotes its inactivation, with cytoplasmic retention. On starvation or lysosomal stress, MTOR inhibition leads to TFE3 dephosphorylation and transcriptional activity. Through this route TFE3 may regulate lysosomal positioning in response to nutrient deprivation by promoting expression of PIP4P1. The same mTOR-dependent control affects pluripotency: TFE3 maintains the pluripotent state of embryonic stem cells by promoting genes such as ESRRB, and is required for the naive pluripotent state of haematopoietic stem cells. Its activity also inhibits neuronal progenitor differentiation and promotes browning of adipose tissue. In association with TFEB, it activates CD40L expression in T-cells, contributing to T-cell-dependent antibody responses and thymus-dependent humoral immunity.
The TFE3 gene encodes a protein that promotes expression of genes downstream of TGF-beta signalling, including COL1A2 through its interaction with TSC22D1 at E-boxes in the proximal promoter. The gene may be involved in chromosomal translocations in renal cell carcinomas and other cancers, producing fusion proteins; partners include PRCC, NONO and ASPSCR1. Alternative splicing results in multiple transcript variants. The mouse ortholog is Tfe3.
TFE3 binds CLEAR-box sequences and activates lysosomal genes, making it a key factor for studying lysosomal biogenesis and the lysosomal stress response.
MTOR phosphorylation controls TFE3 inactivation and cytoplasmic retention, so TFE3 is a readout of amino acid availability and starvation responses.
TFE3 maintains the pluripotent state of embryonic and haematopoietic stem cells, and its mTOR-dependent retention promotes exit from pluripotency.
TFE3 gene fusions with partners such as PRCC, NONO and ASPSCR1 are linked to renal cell carcinomas and other cancers.
TFE3 is a transcription factor that acts as a master regulator of lysosomal biogenesis and immune response. It binds E-box and CLEAR-box sequences, activating lysosomal genes. Its activity is controlled by MTOR: phosphorylation inactivates it in nutrient-rich conditions, and dephosphorylation activates it on starvation or lysosomal stress.
TFE3 is the symbol for transcription factor binding to IGHM enhancer 3, also called transcription factor E3, TFEA and bHLHe33. It belongs to the MiT/TFE family and the basic helix-loop-helix gene group, and dimerises with itself or with family members such as TFEB or MITF. Alternative splicing gives multiple transcript variants.
The TFE3 gene may be involved in chromosomal translocations in renal cell carcinomas and other cancers, forming fusion proteins with partners such as PRCC, NONO and ASPSCR1. A mouse ortholog, Tfe3, exists. Check the datasheet of any product for its validated reactivity.
Other MiT/TFE family members and lysosomal transcription factors that act alongside TFE3.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P19532; product specifications from Assay Genie datasheets.