Transcription factor that acts as a master regulator of melanocyte survival and differentiation as well as melanosome biogenesis ( , ). Binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoter of pigmentation genes, such as tyrosinase (TYR) ( , ). Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, MITF phosphorylation by MTOR promotes its inactivation . Upon starvation or lysosomal stress, inhibition of MTOR induces MITF dephosphorylation, resulting in transcription factor activity . Plays an important role in melanocyte development by regulating the expression of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1) ( , ). Plays a critical role in the differentiation of various cell types, such as neural crest-derived melanocytes, mast cells, osteoclasts and optic cup-derived retinal pigment epithelium ( , ).
Subcellular locations: Nucleus, Cytoplasm, Lysosome membrane
When nutrients are present, recruited to the lysosomal membrane via association with GDP-bound RagC/RRAGC (or RagD/RRAGD): it is then phosphorylated by MTOR (, ). Phosphorylation by MTOR promotes ubiquitination and degradation . Conversely, inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation and translocation to the nucleus . Phosphorylation by MARK3/cTAK1 promotes association with 14-3-3/YWHA adapters and retention in the cytosol .
Expressed in melanocytes (at protein level).
Expressed in the retinal pigment epithelium, brain, and placenta . Expressed in the kidney (, ).
Expressed in the kidney and retinal pigment epithelium.
Expressed in the kidney.
Expressed in the kidney.
Expressed in melanocytes.
Expressed in melanocytes.