MITF (microphthalmia-associated transcription factor) is a transcription factor that activates the transcription of melanocyte-specific genes []. It is also involved in melanocyte differentiation, proliferation, and apoptosis [, , , , ]. MITF has a basic-helix-loop-helix-leucine zipper (bHLHZip) structure; its leucine zipper appears to be essential for dimerisation and DNA binding []. MITF also has important roles in osteoclast and mast cell development and function [, ]. Mutations of the MITF gene are associated with Waardenburg syndrome type 2 (WS2) [, ]and and albinism-deafness (Tietz) syndrome [].
The MiT/TFE family of basic helix-loop-helix leucine zipper transcription factors includes MITF (microphthalmia-associated transcription factor) and related family members TFE3, TFEB and TFEC []. The transcription factors heterodimerize with each other and recognise the same DNA sequences []. They recognise and bind E-box sequences (3'-CANNTG-5').This entry represents transcription factor EC (TFEC). TFEC can act as a repressor or an activator. It acts as a transcriptional repressor on minimal promoter containing muE3 enhancer sequence []and as a transcriptional transactivator on the proximal promoter region of the tartrate-resistant acid phosphatase (TRAP) E-box containing promoter []. It binds DNA in a homo or heterodimeric form with MITF and TFE3.
This entry represents a domain found at the N terminus of the MiT/TFE family members, which include MITF (microphthalmia-associated transcription factor) and its related family members TFE3, TFEB and TFEC []. They are basic helix-loop-helix leucine zipper transcription factors found in chordata. These transcription factors heterodimerize with each other and bind to the E-box core sequence (3'-CANNTG-5') [, ].
This entry represents the lysyl-tRNA synthetase (LysRS) binding domain of AIMP2 (aminoacyl tRNA synthase complex-interacting multifunctional protein 2). LysRS can serve as a transcription regulator that can be released from the cytoplasmic multi-tRNA synthetase complex (MSC) to activate the transcription factor MITF in stimulated mast cells. In quiescent cells, LysRS is held in the MSC via its interactions with AIMP2 [].
This entry represents a domain found at the C terminus of the MiT/TFE family members, which include MITF (microphthalmia-associated transcription factor) and its related family members TFE3, TFEB and TFEC []. They are basic helix-loop-helix leucine zipper transcription factors found in chordata. These transcription factors heterodimerize with each other and bind to the E-box core sequence (3'-CANNTG-5') [, ].
The MiT/TFE family of basic helix-loop-helix leucine zipper transcription factors includes MITF (microphthalmia-associated transcription factor) and related family members TFE3, TFEB and TFEC []. The transcription factors heterodimerize with each other and recognise the same DNA sequences []. They recognise and bind E-box sequences (3'-CANNTG-5').In association with TFE3, TFEB activates the expression of CD40L in T-cells, thereby playing a role in T-cell-dependent antibody responses in activated CD4+ T-cells and thymus-dependent humoral immunity []. It also plays a role in the signal transduction processes required for normal vascularisation of the placenta [].
The MiT/TFE family of basic helix-loop-helix leucine zipper transcription factors includes MITF (microphthalmia-associated transcription factor) and related family members TFE3, TFEB and TFEC []. The transcription factors heterodimerize with each other and recognise the same DNA sequences []. They recognise and bind E-box sequences (3'-CANNTG-5').This entry represents the transcription factor E3 (TFE3). In association with TFEB, TFE3 activates the expression of CD40L in T-cells, thereby playing a role in T-cell-dependent antibody responses in activated CD4+ T-cells and thymus-dependent humoral immunity. It also has also a role in osteoclast development []. TFE3 specifically recognises the MUE3 box, a subset of E-boxes, present in the immunoglobulin enhancer []. For efficient DNA-binding, TFE3 requires dimerisation with itself or with another MiT/TFE family member, such as TFEB or MITF.
p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines []. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease [, ].Vertebrates contain four p38 kinases, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns.p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis []. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway []. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf [].
