MiT Family Transcriptional Factors in Immune Cell Functions

Abstract

The microphthalmia-associated transcription factor family (MiT family) proteins are evolutionarily conserved transcription factors that perform many essential biological functions. In mammals, the MiT family consists of MITF (microphthalmiaassociated transcription factor or melanocyte-inducing transcription factor), TFEB (transcription factor EB), TFE3 (transcription factor E3), and TFEC (transcription factor EC). These transcriptional factors belong to the basic helix-loophelix-leucine zipper (bHLH-LZ) transcription factor family and bind the E-box DNA motifs in the promoter regions of target genes to enhance transcription. The best studied functions of MiT proteins include lysosome biogenesis and autophagy induction. In addition, they modulate cellular metabolism, mitochondria dynamics, and various stress responses. The control of nuclear localization via phosphorylation and dephosphorylation serves as the primary regulatory mechanism for MiT family proteins, and several kinases and phosphatases have been identified to directly determine the transcriptional activities of MiT proteins. In different immune cell types, each MiT family member is shown to play distinct or redundant roles and we expect that there is far more to learn about their functions and regulatory mechanisms in host defense and inflammatory responses.

p38 MAPK‐dependent phosphorylation of TFEB promotes monocyte‐to‐macrophage differentiation

“…In addition to its role in lysosomal biogenesis and autophagy, TFEB has been described to participate in the control of inflammation and host defense against pathogen infection (Visvikis et al , 2014; Brady et al , 2018; Kim et al , 2021), either directly by regulating expression of pro‐inflammatory cytokine and chemokine genes (Visvikis et al , 2014; Pastore et al , 2016), or indirectly by modulating cellular processes that impact the inflammatory response (Irazoqui, 2020; Rawat & Manjithaya, 2021). However, the contribution of TFEB to these processes seems to be context‐specific, where host effectors induce TFEB activation to restrict the intracellular growth of the pathogens (Rawat & Manjithaya, 2021) whereas some pathogens inhibit TFEB activation to facilitate evasion from the host immune response (Irazoqui, 2020).…”

Revealing mitf functions and visualizing allografted tumor metastasis in colorless and immunodeficient Xenopus tropicalis

“…In humans, the MITF locus also plays a crucial role in in the development and function of various immunocytes, such as dendritic cells, B cells, and mast cells 69 . The mitf locus in Xenopus tropicalis is hypothesized to share similarities with the Mitf locus in mammals, allowing for the transcription of multiple isoforms, each exhibiting distinct expression patterns and functions.…”

“…The mitf locus in Xenopus tropicalis is hypothesized to share similarities with the Mitf locus in mammals, allowing for the transcription of multiple isoforms, each exhibiting distinct expression patterns and functions. In mammals, it is well-established that Mitf is also expressed in mast cells, and various mast cell defects have been observed in several Mitf mutant mouse strains 69 . Mitf plays a pivotal role in guiding the differentiation of pre-BMPs (pre-basophil and mast cell progenitors) into mast cells 69 .…”

Emerging roles of TFE3 in metabolic regulation

“…TFE3 DIRECTLY REGULATES THE METABOLISM OF HEPATOCYTES, SKELETAL MUSCLE CELLS, ADIPOCYTES, AND TUMOR CELLS TFE3 plays an important role in the regulation of glucose and lipid metabolism in the body TFE3 is a bHLH transcription factor that binds to E-box sequences [16]. E-box is a gene segment that is involved in several metabolism-related processes, such as glycolysis, insulin signaling, and lipid metabolism [17][18][19].…”