TFEBS211A

TFEBS211A is a constitutively active, nuclear-localized mutant form of the Transcription Factor EB (TFEB). TFEB is a master regulator of the Coordinated Lysosomal Expression and Regulation (CLEAR) network, controlling genes involved in autophagy and lysosomal biogenesis. The S211A mutation involves the substitution of Serine at position 211 with Alanine, which prevents phosphorylation by mTORC1. Since phosphorylation at this site is required for 14-3-3 protein binding and subsequent cytoplasmic sequestration, the S211A mutant remains localized in the nucleus regardless of nutrient status or mTORC1 activity. In the context of oncology research, particularly in Acute Myeloid Leukemia (AML), TFEBS211A has been shown to function as a tumor suppressor by inducing the expression of IDH1 and IDH2, leading to increased levels of alpha-ketoglutarate and global DNA hydroxymethylation. This epigenetic reprogramming promotes terminal myeloid differentiation and apoptosis in leukemia cells, antagonizing the oncogenic effects of MYC.

Other names

TFEB S211ATranscription factor EB S211A