TFEB protein, Human (N-His)

TFEB protein operates as a key transcription factor orchestrating diverse cellular processes, including lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism, and immune response. Recognizing E-box sequences, TFEB's efficient DNA-binding necessitates dimerization with itself or other MiT/TFE family members like TFE3 or MITF. It responds to amino acid availability through MTOR-mediated phosphorylation, promoting cytosolic retention and inactivation. Conversely, MTOR inhibition during starvation or lysosomal stress induces TFEB dephosphorylation, leading to nuclear localization and transcriptional activation. TFEB specifically binds CLEAR-box sequences, activating the expression of lysosomal genes and regulating lysosomal positioning. Additionally, it positively regulates autophagy, contributes to T-cell-dependent antibody responses, and plays a role in vascularization of the placenta. In response to bacterial infection, TFEB mediates itaconate-induced alkylation, activating lysosomal biogenesis and aiding in bacterial clearance. Notably, the eltrombopag drug inhibits TFEB by binding to the bHLH domain and disrupting DNA-binding.