| 背景 | Transcription factor EB (TFEB) is a ~52 kDa protein. Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response. Specifically recognizes and binds E-box sequences (5'-CANNTG-3'); efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFE3 or MITF. Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, TFEB phosphorylation by MTOR promotes its cytosolic retention and subsequent inactivation. Upon starvation or lysosomal stress, inhibition of MTOR induces TFEB dephosphorylation, resulting in nuclear localization and transcription factor activity. Specifically recognizes and binds the CLEAR-box sequence (5'-GTCACGTGAC-3') present in the regulatory region of many lysosomal genes, leading to activate their expression, thereby playing a central role in expression of lysosomal genes. 1. Settembre, C. et al. (2011) Science (New York, N.Y.) 332, 1429-33. PMID: 216170402. Settembre, C. et al. (2012) The EMBO journal 31, 1095-108. PMID: 223439434. Roczniak-Ferguson, A. et al. (2012) Science signaling 5, ra42. PMID: 226924235. Medina, DL. et al. (2015) Nature cell biology 17, 288-99. PMID: 257209636. Napolitano, G. et al. (2018) Nature communications 9, 3312. PMID: 301202337. Lawrence, RE. et al. (2019) Science (New York, N.Y.) 366, 971-977. PMID: 316729139. Kumar, S. et al. (2020) Nature cell biology 22, 973-985. PMID: 3275367210. Zhang, Z. et al. (2022) Molecular cell 82, 2844-2857.e10. PMID: 35662396 |
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