Transcription Factor TFEB Affect The Expression Of Cytokine And The Mechanism Research

TFEB(transcription factor EB) is a member of MiTF/TFE family, which belongs to basic helix-loop-helix-leucine zipper (bHLHZip) transcription factor subfamily. In early studies, TFEB was identified to play a critical role in angiogenesis in embryo development. At present, more and more functions of TFEB have been discovered. And many lysosomal genes exhibiting coordinated transcriptional behavior are regulated by TFEB, so TFEB could affect lysosomal biogenesis and autophagy. TFEB regulates lysosomal exocytosis and then modulates cellular clearance. Thus, TFEB is one of therapeutic targets for Lysosomal Storage Disorders (LSDs), such as Pompe Disease. Because of its critical function, TFEB has to be tightly regulated. The phosphorylation of TFEB is regulated by many proteins through altering its cell location and controlling its function. It has been reported that PGC1? and GCN5L1 could affect the transcription activation of TFEB. And then TFEB's functions could be tightly controlled.We found that mRNA expression of cytokine declines when TFEB-knocking down cells are stimulated with LPS or IL-1?. That may suggests TFEB could promote cytokine expression and enhance immune responses. In mechanism research, TFEB didn't affect phosphorylation and activation of p38, JNK, ERK, and the degradation of I?B?, although TFEB can interact with TRAF6, which is a key factor in NF-?B and MAPK pathway. Therefore, TFEB didn't depend on TRAF6, when affecting cytokine expression. Next, we found that TFEB can bind with p65. They have co-localization in nucleus after TNFa stimulation. Overexpression of TFEB can suppress the influence of p65 on NF-?B-luciferase activity. Thus we put forward a hypothesis that TFEB may show its function after its translocation into nucleus and more detailed molecular machanism still needs to be explored.