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Beschreibung

Transcription factor EB (UniProt: P19484, also known as Class E basic helix-loop-helix protein 35, bHLHe35) is encoded by the TFEB (also known as BHLHE35) gene (Gene ID: 7942) in human. TFEB is a basic Helix-Loop-Helix (bHLH) leucine zipper transcription factor that plays a major role in the regulation of lysosomal biogenesis. TFEB is also a main player in the transcriptional response to starvation and controls autophagy by positively regulating autophagosome formation and autophagosome-lysosome fusion. TFEB is phosphorylated by mTORC1 and ERK at Ser142, which prevents its nuclear translocation. Pharmacological inhibition of mTORC1, as well as starvation and lysosomal disruption, activates TFEB nuclear translocation. Similarly, the serine-threonine kinase RIP1/RIPK1 is shown to suppress basal autophagic flux by activating ERK, which in turn phosphorylates TFEB at Ser142 and thereby prevents TFEB-mediated transcription of gene products involved in autophagy.