text: Most transcription factors function in cooperation with other factors by protein–protein interactions. Association of MITF with other proteins is a critical step in the regulation of MITF-mediated transcriptional activity. Some commonly studied MITF interactions include those with MAZR, PIAS3, Tfe3, hUBC9, PKC1, and LEF1. Looking at the variety of structures gives insight into MITF's varied roles in the cell.
  The Myc-associated zinc-finger protein related factor (MAZR) interacts with the Zip domain of MITF. When expressed together, both MAZR and MITF increase promoter activity of the mMCP-6 gene. MAZR and MITF together transactivate the mMCP-6 gene. MAZR also plays a role in the phenotypic expression of mast cells in association with MITF.
  PIAS3 is a transcriptional inhibiter that acts by inhibiting STAT3's DNA binding activity. PIAS3 directly interacts with MITF, and STAT3 does not interfere with the interaction between PIAS3 and MITF. PIAS3 functions as a key molecule in suppressing the transcriptional activity of MITF. This is important when considering mast cell and melanocyte development.
  MITF, TFE3 and TFEB are part of the basic helix-loop-helix-leucine zipper family of transcription factors. Each protein encoded by the family of transcription factors can bind DNA. MITF is necessary for melanocyte and eye development and new research suggests that TFE3 is also required for osteoclast development, a function redundant of MITF. The combined loss of both genes results in severe osteopetrosis, pointing to an interaction between MITF and other members of its transcription factor family. In turn, TFEB has been termed as the master regulator of lysosome biogenesis and autophagy.  Interestingly, MITF, TFEB and TFE3 separate roles in modulating starvation-induced autophagy have been described in melanoma. Moreover, MITF and TFEB proteins, directly regulate each other’s mRNA and protein expression while their subcellular localization and transcriptional activity are subject to similar modulation, such as the mTOR signaling pathway.
  UBC9 is a ubiquitin conjugating enzyme whose proteins associates with MITF. Although hUBC9 is known to act preferentially with SENTRIN/SUMO1, an in vitro analysis demonstrated greater actual association with MITF.  hUBC9 is a critical regulator of melanocyte differentiation. To do this, it targets MITF for proteasome degradation.
  Protein kinase C-interacting protein 1 (PKC1) associates with MITF. Their association is reduced upon cell activation. When this happens MITF disengages from PKC1. PKC1 by itself, found in the cytosol and nucleus, has no known physiological function. It does, however, have the ability to suppress MITF transcriptional activity and can function as an in vivo negative regulator of MITF induced transcriptional activity.
  The functional cooperation between MITF and the lymphoid enhancing factor (LEF-1) results in a synergistic transactivation of the dopachrome tautomerase gene promoter, which is an early melanoblast marker. LEF-1 is involved in the process of regulation by Wnt signaling. LEF-1 also cooperates with MITF-related proteins like TFE3. MITF is a modulator of LEF-1, and this regulation ensures efficient propagation of Wnt signals in many cells.