Microphthalamia-associated transcription factor: a critical regulator of pigment cell development and survival

Widlund, Hans R.; Fisher, David E.

doi:10.1038/sj.onc.1206443

Cited by 326 publications

(237 citation statements)

References 88 publications

Supporting

Mentioning

227

Contrasting

Unclassified

Order By: Relevance

“…Instead, MITF deficiency produces depigmentation due to absence of viable melanocytes. [8][9][10] Interestingly, besides its role in melanocyte survival/ proliferation, it is also clear that MITF transcriptionally regulates expression of numerous pigmentation genes. Thus, MITF appears to be a master regulator of melanocyte development, differentiation, migration, survival and function.…”

Section: Dual Roles Of Lineage Restricted Transcription Factorsmentioning

confidence: 99%

Dual roles of lineage restricted transcription factors

Levy

Fisher

2011

Transcription

View full text Add to dashboard Cite

m i c r o p h t h a l m i a -a s s o c i a t e d transcription factor, mitf, is a master regulator of melanocyte development, differentiation, migration and survival. 1 a broad collection of studies have indicated that mitf directly regulates the transcription of genes involved in pigmentation, which are selective to the melanocyte lineage. in addition, mitf controls expression of genes which are expressed in multiple cell lineages and may also play differential roles in activating vs. maintaining gene expression patterns. in this point-of-view article, we discuss lineage restricted transcription factor activation of both tissue-specific and ubiquitously expressed genes using melanocytes and mitf as a model system that may eventually provide insights into such processes in multiple cell lineages.Cell reprogramming, where the epigenetic signature directing cellular identity can be erased and rewritten, demonstrates the pervasive and far-reaching importance of transcription factors in the development, maintenance and rewiring of cells.2 In 2006, Takahashi and Yamanaka published their seminal study on cell reprogramming, showing that only four selected transcription factors were required to directly and permanently transform adult mouse fibroblasts into induced pluripotent stem (iPS) cells.3,4 However, reprogramming can also include the conversion of one somatic cell type to another.In 1996, it was shown that ectopic expression of a single transcription factor, MITF, may convert fibroblasts into cells with characteristics of pigment-producing dual roles of lineage restricted transcription factors

show abstract

Section: Dual Roles Of Lineage Restricted Transcription Factorsmentioning

confidence: 99%

Dual roles of lineage restricted transcription factors

Levy

Fisher

2011

Transcription

View full text Add to dashboard Cite

show abstract

“…For example, α-melanocyte-stimulating hormone strongly increases MITF expression through a cyclic AMP and CREB/ATF1-mediated pathway [6][7][8] . In addition, through its melanocyte-specific promoter (M-MITF), the expression of MITF is regulated by paired box gene 3 (PAX3), SRY (sex-determining region Y)-box 10 (SOX10), lymphoid enhancerbinding factor 1 (LEF1), and one cut domain 2 (ONECUT-2) [9][10][11][12] In Clear Cell Sarcoma the EWS-ATF1 fusion oncoprotein occupies the MITF promoter, constitutively replaces the cAMP-driven activity of CREB/ATF1soasto mimicking melanocyte-stimulating hormone signalling to induce expression of MITF 13 . In this kind of tumour MITF appears to have an oncogenic role as well 13 .…”

mentioning

confidence: 99%

Regulation of MITF stability by the USP13 deubiquitinase

et al. 2011

Self Cite

View full text Add to dashboard Cite

The microphthalmia-associated transcription factor (MITF) is essential for melanocyte development. Mutation-induced MAPK pathway activation is common in melanoma and induces MITF phosphorylation, ubiquitination, and proteolysis. Little is known about the enzymes involved in MITF ubiquitination/deubiquitination. Here we report the identification of a deubiquitinating enzyme, named ubiquitin-specific protease 13 (USP13) that appears to be responsible for MITF deubiquitination, utilizing a short hairpin RNA library against known deubiquitinating enzymes. Through deubiquitination, USP13 stabilizes and upregulates MITF protein levels. Conversely, suppression of USP13 (through knockdown) leads to dramatic loss of MITF protein, but not messenger RNA. Through its effects on MITF deubiquitination, USP13 was observed to modulate expression of MITF downstream target genes and, thereby, to be essential for melanoma growth in soft agar and in nude mice. These observations suggest that as a potentially drugable protease, USP13 might be a viable therapeutic target for melanoma.

show abstract

“…MITF controls expression of several proteins required for melanin synthesis, including tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and dopachrome tautomerose (DCT) (1)(2)(3). In addition, MITF plays a critical role in melanocyte survival and serves as a lineagespecific oncogene in melanoma, as evidenced by its amplification in a subset of melanomas (4)(5)(6). MITF expression is regulated by several factors, including SOX-10, CREB, PAX3, LEF1, and ATF2 (7,8).…”

mentioning

confidence: 99%

“…MITF expression is regulated by several factors, including SOX-10, CREB, PAX3, LEF1, and ATF2 (7,8). MITF in turn regulates a plethora of genes, with its complex role in melanoma biology, as its overexpression has been shown to result in both proproliferative and antiproliferative stimuli (4,5,9,10). Accordingly, verified targets of MITF include both genes that promote cell survival and block apoptosis, (e.g., CDK2, BCL2, DIAPH1, and TBX2), and genes that block cell cycle progression (e.g., CDKN2A and p21Cip1).…”

mentioning

confidence: 99%

BPTF transduces MITF-driven prosurvival signals in melanoma cells

Dar

Majid

Bezrookove

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Microphthalmia-associated transcription factor (MITF) plays a critical and complex role in melanocyte transformation. Although several downstream targets of MITF action have been identified, the precise mechanisms by which MITF promotes melanocytic tumor progression are incompletely understood. Recent studies identified an oncogenic role for the bromodomain plant homeodomain finger transcription factor (BPTF) gene in melanoma progression, in part through activation of BCL2, a canonical target of MITF signaling. Analysis of the BPTF promoter identified a putative MITF-binding site, suggesting that MITF may regulate BPTF expression. Overexpression of MITF resulted in up-regulation of BPTF in a panel of melanoma and melanocyte cell lines. shRNA-mediated down-regulation of MITF in melanoma cells was accompanied by down-regulation of BPTF and BPTF-regulated genes (including BCL2) and resulted in reduced proliferative capacity of melanoma cells. The suppression of cell growth mediated by MITF silencing was rescued by overexpression of BPTF cDNA. Binding of MITF to the BPTF promoter was demonstrated using ChIP analysis. MITF overexpression resulted in direct transcriptional activation of BPTF, as evidenced by increased luciferase activity driven by the BPTF promoter. These results indicate that BPTF transduces key prosurvival signals driven by MITF, further supporting its important role in promoting melanoma cell survival and progression. melanoma | signaling cascade | oncogenes M icrophthalmia-associated transcription factor (MITF) is known to play a key role in melanocyte biology and progression. MITF performs these functions by activating transcription of many genes through interaction with the consensus DNA-binding sequence (CACGTG, termed E box) present on the promoters of target genes. MITF controls expression of several proteins required for melanin synthesis, including tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and dopachrome tautomerose (DCT) (1-3). In addition, MITF plays a critical role in melanocyte survival and serves as a lineagespecific oncogene in melanoma, as evidenced by its amplification in a subset of melanomas (4-6). MITF expression is regulated by several factors, including SOX-10, CREB, PAX3, LEF1, and ATF2 (7,8). MITF in turn regulates a plethora of genes, with its complex role in melanoma biology, as its overexpression has been shown to result in both proproliferative and antiproliferative stimuli (4, 5, 9, 10). Accordingly, verified targets of MITF include both genes that promote cell survival and block apoptosis, (e.g., CDK2, BCL2, DIAPH1, and TBX2), and genes that block cell cycle progression (e.g., CDKN2A and p21Cip1). Thus, although several downstream targets of MITF action have been identified, the precise mechanisms by which MITF promotes melanocytic tumor progression are still poorly understood.Recently, we identified a role for the bromodomain plant homeodomain finger transcription factor (BPTF) gene in melanoma progression (11). BPTF is the largest subunit of the nucleoso...

show abstract

Microphthalamia-associated transcription factor: a critical regulator of pigment cell development and survival

Cited by 326 publications

References 88 publications

Dual roles of lineage restricted transcription factors

Dual roles of lineage restricted transcription factors

Regulation of MITF stability by the USP13 deubiquitinase

BPTF transduces MITF-driven prosurvival signals in melanoma cells

Contact Info

Product

Resources

About