MITF-M dimer binds the TBX2 gene

Stable Identifier
R-HSA-9825845
Type
Reaction [binding]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
MITF-M dimer binds the TBX2 gene
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
TBX2 (T-box transcription factor 2) is a member of the T-box family of transcription factors that play a role in establishing cell identity during embryonic development and contribute to the development of cancer (reviewed in Abrahams et al, 2010; Niu et al, 2021). TBX2 is expressed in melanoblasts and melanocytes but is not expressed in melanoblast precursors of the neural crest, and its expression may therefore be linked to establishment and maintenance of melanocyte lineage identity (Carreira et al, 1998). TBX2 is also expressed in a number of MITF-expressing melanoma cell lines but not in the MITF-negative K1735 cell line (Carreira et al, 2000).
Analysis of the TBX2 promoter in mouse has identified an E-box element between positions-332 and -327 that drives MITF-dependent reporter gene expression and is bound by MITF in electrophoretic mobility shift assay (EMSA) (Carreira et al, 2000). Consistent with this, TBX2 was identified as a direct MITF target in human melanoma lines by ChIP-seq (Strub et al, 2011).
TBX2 is a negative regulator of TYRP1 gene expression. TYRP1 contributes both to the enzymatic steps of melanin synthesis and has also been implicated in the regulation of melanocyte proliferation (Carreira et al, 1998; Sarangarajan et al, 2000; reviewed in Cheli et al, 2010). TBX2 may additionally impact MITF-dependent proliferation and cell cycle by virtue of its activation of Cyclin D expression as demonstrated in mouse melanocytes, as well as by repressing expression of the cell cycle inhibitors CDKN1A (p21) and the CDKN2A gene-protein product p14ARF (p19 ARF in mouse) (Pan et al, 2015; Jacobs et al, 2000; Prince et al, 2004; Vance et al, 2005; reviewed in Cheli et al, 2010).
Literature References
PubMed ID Title Journal Year
10770922 The gene encoding the T-box factor Tbx2 is a target for the microphthalmia-associated transcription factor in melanocytes

Liu, B, Goding, CR, Carreira, S

J Biol Chem 2000
11041210 Mutant alleles at the brown locus encoding tyrosinase-related protein-1 (TRP-1) affect proliferation of mouse melanocytes in culture

Babcock, G, Sarangarajan, R, Boissy, RE, Zhao, Y, Lamoreux, ML, Cornelius, J

Pigment Cell Res 2000
9710594 Brachyury-related transcription factor Tbx2 and repression of the melanocyte-specific TRP-1 promoter

Easty, DJ, Goding, CR, Dexter, TJ, Yavuzer, U, Carreira, S

Mol Cell Biol 1998
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
34897787 Role of T-box genes in cancer, epithelial-mesenchymal transition, and cancer stem cells

Sheng, S, Niu, G, Wen, F, Hao, J

J Cell Biochem 2022
14996726 Tbx2 directly represses the expression of the p21(WAF1) cyclin-dependent kinase inhibitor

Prince, S, Abrahams, A, Carreira, S, Vance, KW, Goding, CR

Cancer Res 2004
19995375 Fifteen-year quest for microphthalmia-associated transcription factor target genes

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

Pigment Cell Melanoma Res 2010
11062467 Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19(ARF)) and is amplified in a subset of human breast cancers

van de Vijver, MJ, van Welsem, T, Kristel, P, Keblusek, P, Jacobs, JJ, Robanus-Maandag, E, Nederlof, PM, Koh, EY, Lingbeek, M, Daley, GQ, van Lohuizen, M

Nat Genet 2000
15781639 Tbx2 is overexpressed and plays an important role in maintaining proliferation and suppression of senescence in melanomas

Carreira, S, Vance, KW, Goding, CR, Brosch, G

Cancer Res 2005
26486273 Microphthalmia-associated transcription factor/T-box factor-2 axis acts through Cyclin D1 to regulate melanocyte proliferation

Chen, Y, Ma, X, Wen, B, Qu, J, Li, H, Liu, Y, Pan, L, Zheng, X, Lu, F, Wang, J, Su, Z, Hou, L

Cell Prolif 2015
19960541 The T-box transcription factor Tbx2: its role in development and possible implication in cancer

Prince, S, Abrahams, A, Parker, MI

IUBMB Life 2010
Participants
Input
Output
Participates
as an event of
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  (2023-01-27)
Cite Us!