Fig. 3.

Mechanisms mediating the regulation of TFEB. (a) Phosphorylation is a well-recognized post-translational modification that regulates TFEB nuclear translocation. Inhibition of mTOR or ERK, activation of PKCβ or activation of phosphatases calcineurin or PP2A induces TFEB nuclear translocation and enhances TFEB transcriptional activity. mTOR or mTORC2-GSK3β facilitates TFEB nuclear export. (b) TFEB expression is regulated at the transcriptional level. Numerous transcription factors, including Krüppel-like factor 2 (KLF2), Forkhead box O1 (FOXO1), cAMP response element-binding protein (CREB) and its co-activator, CREB-regulated transcription co-activator 2 (CRTC2), peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and TFEB itself, transactivate TFEB gene expression. Also, methyltransferase like 3 (METTL3) decreases TFEB mRNA expression by N6-methyladenosine (m6A) modification.