TFEB

Transcription factor EB is a is_associated_with::protein that in humans is encoded by the TFEB is_associated_with::gene.

Function
TFEB is a master gene for lysosomal is_associated_with::biogenesis. It encodes a is_associated_with::transcription factor that coordinates expression of lysosomal hydrolases, membrane proteins and genes involved in is_associated_with::autophagy. Under aberrant lysosomal storage conditions such as in is_associated_with::lysosomal storage diseases, TFEB translocated from the cytoplasm to the nucleus, resulting in the activation of its target genes. TFEB overexpression in cultured cells induced lysosomal biogenesis and increased the degradation of complex molecules, such as glycosaminoglycans and the pathogenic protein that causes Huntington disease. TFEB is activated by PGC1-alpha and promotes reduction of htt aggregation and neurotoxicity in a mouse model of Huntington disease. Nuclear localization and activity of TFEB are regulated by serine phosphorylation and extracellular signal–regulated kinase 2 (ERK2) is the enzyme that phosphorylates TFEB. In turn, ERK2 is tuned to the levels of extracellular nutrients suggesting a coordination in regulation of autophagy and lysomal biogenesis and partnership of two distinct cellular organelles. TFEB is activated in Trex1-deficient cells via inhibition of mTORC1 activity, resulting in an expanded lysosomal compartment.