Expression of Tyrosinase-related Protein 2/DOPAchrome Tautomerase in the Retinoblastoma

Udono, Tetsuo; Takahashi, Kazuhiro; Yasumoto, Ken Ichi; Yoshizawa, Miki; Takeda, Kazuhisa; Abe, Toshiaki; Tamai, Makoto; Shibahara, Shigeki

doi:10.1006/exer.2000.0948

Cited by 17 publications

(12 citation statements)

References 46 publications

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“…Transient expression assays were performed in ARPE‐19 human RPE cells that express DCT (Udono et al . ) and tyrosinase (unpublished results). No significant increase in luciferase activity was detected with each aberrant Mitf‐M protein, except for Mitf (del 3) that significantly increased the luciferase activity (Fig.…”

Section: Resultsmentioning

confidence: 72%

Insertion of long interspersed element‐1 in theMitfgene is associated with altered neurobehavior of the black‐eyed whiteMitf^mi‐bwmouse

et al. 2013

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Microphthalmia-associated transcription factor (Mitf) is required for the differentiation of melanoblasts of the neural crest origin. The mouse homozygous for the black-eyed white (Mitf mi-bw ) allele is characterized by white-coat color and deafness with black eye, due to the loss of melanoblasts during embryonic development. The Mitf mi-bw allele carries an insertion of long interspersed element-1 (L1) in intron 3 of the Mitf gene, which may cause the deficiency of melanocyte-specific Mitf-M. Here, we show that the L1 insertion results in the generation of alternatively spliced Mitf-M mRNA species, such as Mitf-M mRNA lacking exon 3, exon 4 or both exons 3 and 4, each of which encodes Mitf-M protein with an internal deletion. Transient expression assays showed the loss of or reduction in function of each aberrant Mitf-M protein and the dominant negative effect of Mitf-M lacking exon 4 that encodes an activation domain. Thus, the L1 insertion may decrease the expression level of functional Mitf-M. Importantly, Mitf-M mRNA is expressed in the wild-type mouse brain, with the highest expression level in the hypothalamus. Likewise, aberrant Mitf-M mRNAs are expressed in the bw mouse brain. The bw mice show the altered neurobehavior under a stressful environment, suggesting the role of Mitf-M in sensory perception.

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Section: Resultsmentioning

confidence: 72%

Insertion of long interspersed element‐1 in theMitfgene is associated with altered neurobehavior of the black‐eyed whiteMitf^mi‐bwmouse

et al. 2013

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“…1992). In this connection, DCT is expressed in certain human tumors comprising undifferentiated cells, such as retinoblastoma (Udono et al. 2001) and glioblastoma multiforme (Suzuki et al.…”

Section: Discussionmentioning

confidence: 99%

Impaired development of melanoblasts in the black‐eyed white Mitf^mi‐bw mouse, a model for auditory–pigmentary disorders

et al. 2012

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Microphthalmia-associated transcription factor (Mitf) is a regulator for differentiation of melanoblasts that are derived from the neural crest. The mouse homozygous for the black-eyed white (Mitf mi-bw ) allele is characterized by the white coat color and deafness, with black eye that is associated with the lack of melanocytes in skin and inner ear. The Mitf mi-bw mutation is an insertion of the LINE1 retrotransposable element into intron 3 of the Mitf gene that causes the selective deficiency of the melanocyte-specific Mitf isoform, Mitf-M. Here, we show the expression of Mitf-M mRNA in the trunk region of the homozygous Mitf mi-bw (bw) mouse at embryonic days (E) 11.5 and E12.5, but Mitf-M mRNA is undetectable at E13.5. In addition, using bw mouse that carries the lacZ transgene under the control of a melanoblast-specific promoter, we show that the number of migrating melanoblasts in bw embryos was less than 10% of that in control embryos at E11.5 and E12.5, and melanoblasts disappear by E13.5. The loss of melanoblasts in bw embryos was probably caused by apoptosis. Finally, forced expression of Mitf-M in the cultured neural tube of bw embryos ensured the differentiation of melanoblasts. Therefore, the correct dose of Mitf-M is required for the normal development of melanoblasts.

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“…The functional importance of this 12‐bp motif is also supported by the presence of the same sequence at the equivalent position of the mouse DCT gene promoter (Budd and Jackson, 1995). In this context, DCT mRNA expression is upregulated by forskolin, a cAMP‐elevating agent, in human melanoma cells (Udono et al ., 2001) and mouse melanoma cells (Bertolotto et al ., 1998), but not in human retinoblastoma cells (Udono et al ., 2001). Future studies will be aimed at exploring the role of cAMP for the observed functional cooperation of MITF‐M, LEF‐1 and the CRE‐like motif‐binding protein.…”

Section: Discussionmentioning

confidence: 99%

Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling

2002

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Wnt signals regulate differentiation of neural crest cells through the b-catenin associated with a nuclear mediator of the lymphoid-enhancing factor 1 (LEF-1)/ T-cell factors (TCFs) family. Here we show the interaction between the basic helix±loop±helix and leucine-zipper region of microphthalmia-associated transcription factor (MITF) and LEF-1. MITF is essential for melanocyte differentiation and its heterozygous mutations cause auditory±pigmentary syndromes. Functional cooperation of MITF with LEF-1 results in synergistic transactivation of the dopachrome tautomerase (DCT) gene promoter, an early melanoblast marker. This activation depends on the separate cis-acting elements, which are also responsible for the induction of the DCT promoter by lithium chloride that mimics Wnt signaling. b-catenin is required for ef®cient transactivation, but dispensable for the interaction between MITF and LEF-1. The interaction with MITF is unique to LEF-1 and not detectable with TCF-1. LEF-1 also cooperates with the MITF-related proteins, such as TFE3, to transactivate the DCT promoter. This study therefore suggests that the MITF/TFE3 family is a new class of nuclear modulators for LEF-1, which may ensure ef®cient propagation of Wnt signals in many types of cells.

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Expression of Tyrosinase-related Protein 2/DOPAchrome Tautomerase in the Retinoblastoma

Cited by 17 publications

References 46 publications

Insertion of long interspersed element‐1 in theMitfgene is associated with altered neurobehavior of the black‐eyed whiteMitf^mi‐bwmouse

Insertion of long interspersed element‐1 in theMitfgene is associated with altered neurobehavior of the black‐eyed whiteMitf^mi‐bwmouse

Impaired development of melanoblasts in the black‐eyed white Mitf^mi‐bw mouse, a model for auditory–pigmentary disorders

Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling

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Expression of Tyrosinase-related Protein 2/DOPAchrome Tautomerase in the Retinoblastoma

Cited by 17 publications

References 46 publications

Insertion of long interspersed element‐1 in theMitfgene is associated with altered neurobehavior of the black‐eyed whiteMitfmi‐bwmouse

Insertion of long interspersed element‐1 in theMitfgene is associated with altered neurobehavior of the black‐eyed whiteMitfmi‐bwmouse

Impaired development of melanoblasts in the black‐eyed white Mitfmi‐bw mouse, a model for auditory–pigmentary disorders

Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling

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Insertion of long interspersed element‐1 in theMitfgene is associated with altered neurobehavior of the black‐eyed whiteMitf^mi‐bwmouse

Insertion of long interspersed element‐1 in theMitfgene is associated with altered neurobehavior of the black‐eyed whiteMitf^mi‐bwmouse

Impaired development of melanoblasts in the black‐eyed white Mitf^mi‐bw mouse, a model for auditory–pigmentary disorders