MITF-M-dependent TYR gene expression

Stable Identifier
R-HSA-9824579
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
nucleoplasm, melanosome membrane
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
MITF-M-dependent TYR gene expression
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
Tyrosinase, encoded by the TYR gene, catalyzes the first two steps in the synthesis of melanin from tyrosine, the conversion of tyrosine to 3,4-dihydroxyphenylalanine (DOPA) and of DOPA to DOPA quinone (reviewed in Cheli et al, 2010). Through reporter gene assays, MITF was identified as a transcriptional activator that stimulates TYR gene expression through an E-box adjacent to the transcriptional start site (Bentley et al, 1994). Subsequent studies demonstrated direct binding of MITF to the TYR promoter in human and mouse in vitro and in vivo (Bertolotto et al, 1996; Bertolotto et al, 1998 a, b; Galibert et al, 2001; Strub et al, 2011). UV-dependent upregulation of MITF appears to additionally depend on the binding of USF1 to the TYR promoter (Bertolotto et al, 1996; Bertolotto et al, 1998 a,b; Takeda et al, 1998; Galibert et al, 2001; Strub et al, 2011; reviewed in Goding and Arnheiter, 2019). MITF-M also recruits the SWI/SNF complex to the promoter, as demonstrated through co-immunoprecipitation of MITF with SWI/SNF components SMARCA4, SMARCE1 and SMARCB1 in mouse (de la Serna et al, 2006). The MITF-M-dependent transcription factor IRF4 also contributes to TYR gene expression, binding to elements in the TYR promoter to stimulate expression in a co-operative manner with MITF-M (Praetorius et al, 2013).
Literature References
PubMed ID Title Journal Year
24267888 A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway

Bergsteinsdóttir, K, Petit, V, Ogmundsdóttir, MH, Stacey, SN, Robinson, KC, Davis, SR, Stefansson, K, Larue, L, Smith, AG, Magnusdottir, E, Cornell, R, Helgason, AS, Adams, DR, Merlino, G, Grill, C, Mishra, PJ, Praetorius, C, Meltzer, PS, Sturm, RA, Mccallion, AS, Emre, NC, Fisher, DE, Guo, T, Metcalf, AM, Kim, RS, Sigurdsson, MI, Sobhiafshar, U, Zaidi, MR, Gorkin, DU, Van Otterloo, E, Pavan, WJ, Loftus, SK, Steingrímsson, E

Cell 2013
7969139 Melanocyte-specific expression of the human tyrosinase promoter: activation by the microphthalmia gene product and role of the initiator

Eisen, T, Bentley, NJ, Goding, CR

Mol Cell Biol 1994
8707852 Regulation of tyrosinase gene expression by cAMP in B16 melanoma cells involves two CATGTG motifs surrounding the TATA box: implication of the microphthalmia gene product

Bille, K, Ballotti, R, Bertolotto, C, Ortonne, JP

J Cell Biol 1996
21258399 Essential role of microphthalmia transcription factor for DNA replication, mitosis and genomic stability in melanoma

Ye, T, Cormont, M, Keime, C, Kobi, D, Davidson, I, Le Gras, S, Giuliano, S, Bonet, C, Bertolotto, C, Ballotti, R, Strub, T

Oncogene 2011
10587587 Ser298 of MITF, a mutation site in Waardenburg syndrome type 2, is a phosphorylation site with functional significance

Tachibana, M, Nobukuni, Y, Watanabe, A, Fisher, DE, Kobayashi, I, Takemoto, C, Takeda, K

Hum Mol Genet 2000
9700169 Microphthalmia gene product as a signal transducer in cAMP-induced differentiation of melanocytes

Hemesath, TJ, Abbe, P, Bille, K, Ballotti, R, Bertolotto, C, Fisher, DE, Ortonne, JP

J Cell Biol 1998
19995375 Fifteen-year quest for microphthalmia-associated transcription factor target genes

Bertolotto, C, Cheli, Y, Ohanna, M, Ballotti, R

Pigment Cell Melanoma Res 2010
31123060 MITF-the first 25 years

Arnheiter, H, Goding, CR

Genes Dev 2019
16648630 The microphthalmia-associated transcription factor requires SWI/SNF enzymes to activate melanocyte-specific genes

Osias, J, Kommajosyula, N, Tachibana, T, Dutta, C, de la Serna, IL, Ohkawa, Y, Imbalzano, AN, Higashi, C

J Biol Chem 2006
9447965 Different cis-acting elements are involved in the regulation of TRP1 and TRP2 promoter activities by cyclic AMP: pivotal role of M boxes (GTCATGTGCT) and of microphthalmia

Abbe, P, Bille, K, Ballotti, R, Bertolotto, C, Ortonne, JP, Buscà, R, Aberdam, E

Mol Cell Biol 1998
11532965 The Usf-1 transcription factor is a novel target for the stress-responsive p38 kinase and mediates UV-induced Tyrosinase expression

Goding, CR, Carreira, S, Galibert, MD

EMBO J 2001
Participants
Input
Output
Participates
as an event of
This event is regulated
Positively by
Regulator
IRF4:TYR gene [nucleoplasm] (Homo sapiens)
Active Unit
IRF4 [nucleoplasm]
Regulator
pT153 USF1 dimer:TYR promoter [nucleoplasm] (Homo sapiens)
Active Unit
pT153 USF1 dimer [nucleoplasm]
Regulator
M-MITF dimer:BAF complex:TYR gene [nucleoplasm] (Homo sapiens)
Active Unit
MITF-M dimer [nucleoplasm]
Authored
Rothfels, K  (2023-01-26)
Reviewed
de la Serna, IL  (2024-05-21)
Arnheiter, H  (2024-02-26)
Steingrímsson, E  (2024-11-05)
Vu, HN  (2024-11-05)
Created
Rothfels, K  (2023-01-20)
Cite Us!