Recombinant Human MiTF protein (GST tag N-Terminus)

Specifications

Form

Liquid

General info

Function

Transcription factor that acts as a master regulator of melanocyte survival and differentiation as well as melanosome biogenesis (PubMed : 10587587, PubMed : 22647378, PubMed : 27889061, PubMed : 9647758). 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) (PubMed : 10587587, PubMed : 22647378, PubMed : 27889061, PubMed : 9647758). 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 (PubMed : 36608670). Upon starvation or lysosomal stress, inhibition of MTOR induces MITF dephosphorylation, resulting in transcription factor activity (PubMed : 36608670). Plays an important role in melanocyte development by regulating the expression of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1) (PubMed : 10587587, PubMed : 22647378, PubMed : 27889061, PubMed : 9647758). 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 (PubMed : 10587587, PubMed : 22647378, PubMed : 27889061, PubMed : 9647758).

Sequence similarities

Belongs to the MiT/TFE family.

Post-translational modifications

When nutrients are present, phosphorylation by MTOR at Ser-5 via non-canonical mTORC1 pathway promotes ubiquitination by the SCF(BTRC) complex, followed by degradation (PubMed:36608670). Phosphorylation at Ser-405 significantly enhances the ability to bind the tyrosinase promoter (PubMed:10587587). Phosphorylation by MARK3/cTAK1 at Ser-280 promotes association with 14-3-3/YWHA adapters and retention in the cytosol (PubMed:16822840). Phosphorylated at Ser-180 and Ser-516 following KIT signaling, triggering a short live activation: Phosphorylation at Ser-180 and Ser-516 by MAPK and RPS6KA1, respectively, activate the transcription factor activity but also promote ubiquitination and subsequent degradation by the proteasome (PubMed:10673502). Phosphorylated in response to blue light (415nm) (PubMed:28842328).. Ubiquitinated by the SCF(BTRC) and SCF(FBXW11) complexes following phosphorylation ar Ser-5 by MTOR, leading to its degradation by the proteasome (PubMed:36608670). Ubiquitinated following phosphorylation at Ser-180, leading to subsequent degradation by the proteasome (PubMed:10673502). Deubiquitinated by USP13, preventing its degradation (PubMed:10673502).