Linkage of M-CSF Signaling to Mitf, TFE3, and the Osteoclast Defect in Mitfmi/mi Mice

Weilbaecher, Katherine N.; Motyckova, Gabriela; Huber, Wade E.; Takemoto, Clifford M.; Hemesath, Timothy J.; Xu, Ying; Hershey, Christine L.; Dowland, Nikki; Wells, Audrey G.; Fisher, David E.

doi:10.1016/s1097-2765(01)00360-4

Cited by 143 publications

(104 citation statements)

References 52 publications

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“…Of note, certain nonmelanocyte lineages, such as osteoclasts, are severely abnormal in mice harboring homozygous dominant-negative MITF mutations, but much less affected by null mutations. This effect is likely because of the ability of dominant-negative MITF mutants that titrate out other MiT family members, such as TFE3 in osteoclasts (Weilbaecher et al, 1998(Weilbaecher et al, , 2001Steingrı´msson et al, 2002).…”

Section: Mitf As a Key Transcription Factor In The Pigment Biosynthesmentioning

confidence: 99%

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

2003

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The microphthalamia-associated transcription factor (MITF) is an integral transcriptional regulator in melanocyte, the lineage from which melanoma cells originate. This basic-helix-loop-helix-leucine-zipper (bHLHzip) protein is critical for melanocyte cell-fate choice during commitment from pluripotent precursor cells in the neural crest. Its role in differentiation pathways has been highlighted by its potent transcriptional and lineage-specific regulation of the three major pigment enzymes: tyrosinase, Tyrp1, and Dct as well as other pigmentation factors. However, the cellular functions of MITF seem to be wider than differentiation and cell-fate pathways alone, since melanocytes and melanoma cells appear to require an expression of this factor. Here, we discuss the transcriptional networks in which MITF is thought to reside and describe signaling pathways in the cell which impinge on MITF. Accumulating evidence supports the notion that MITF is involved in survival pathways during normal development as well as during neoplastic growth of melanoma.

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Section: Mitf As a Key Transcription Factor In The Pigment Biosynthesmentioning

confidence: 99%

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

2003

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“…It has also been shown that TFE3 binds the co-activator p300 in vivo (49). It was suggested that the precise E-box⅐TFE3, SBE⅐Smad, and TFE3⅐Smad interaction arrangements on the PAI-1 promoter allow for efficient recruitment of either CBP or p300 coactivator leading to enhanced transcription (26).…”

Section: Bcn-1 Element-dependent Activation Of the Laminin ␥1 Chain Genementioning

confidence: 99%

“…The heterodimer translocates to the nucleus where it binds one of the 5Ј SBE elements of the LAMC1 promoter that is appropriately bent by TFE3 and other DNA-bending factors. The interaction of TFE3 with the Smad heterodimer that follows generates a constructive topology for an effective recruitment of co-activators, such as CBP (33,49), and basal transcriptional machinery leading to enhanced LAMC1 gene transcription.…”

Section: Bcn-1 Element-dependent Activation Of the Laminin ␥1 Chain Genementioning

confidence: 99%

bcn-1 Element-dependent Activation of the Laminin γ1 Chain Gene by the Cooperative Action of Transcription Factor E3 (TFE3) and Smad Proteins

Kawata¹,

Suzuki²,

Higaki

et al. 2002

Journal of Biological Chemistry

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Laminin is a major component of the extracellular matrix. The laminin ␥1 chain is the least variant component of the laminin heterotrimeric assembly. The laminin ␥1 chain gene (LAMC1) expression is induced by several factors, including transforming growth factor-␤ (TGF-␤). LAMC1 promoter contains a highly conserved transcriptional element, bcn-1. We screened cDNA libraries with the yeast one-hybrid system to identify transcriptional factors that are recognized by the bcn-1 motif. Using this strategy we isolated the basic helixloop-helix/leucine zipper (bHLHzip) E-box-binding transcription factor, TFE3. Until now, the E-box was the only element known to recruit the bHLHzip transcription factors. Although the bcn-1 element only remotely resembles the E-box sequence, we show that TFE3 binds and activates the bcn-1 element. TFE3 cooperates with Smad proteins in the activation of the LAMC1 promoter in cells, an effect that is critically dependent not only on the bcn-1 element but also on one of the Smad-binding elements (SBE). The cooperative induction of the LAMC1 promoter and the endogenous LAMC1 gene by TFE3 and Smad3 is augmented by the TGF-␤ signaling pathway. Thus, the bcn-1 is a novel TFE3-dependent TGF-␤ target element that regulates LAMC1 gene expression.

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“…Mice homozygous null for TFE3 or TFEC had no recognized abnormalities (8), but TFEB nulls exhibited embryonic lethality associated with placental vascular defects (12). In addition, Mitf and TFE3 have been found to undergo identical modifications after cytokine stimulation (13), and MITF has been shown to directly regulate BCL2, a key apoptotic regulator, in a manner important for melanocyte and melanoma survival (14).…”

mentioning

confidence: 99%

Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation

Davis

Hsi

Arroyo

et al. 2003

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

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227

173

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MITF, TFE3, TFEB, and TFEC comprise a transcription factor family (MiT) that regulates key developmental pathways in several cell lineages. Like MYC, MiT members are basic helix-loop-helix-leucine zipper transcription factors. MiT members share virtually perfect homology in their DNA binding domains and bind a common DNA motif. Translocations of TFE3 occur in specific subsets of human renal cell carcinomas and in alveolar soft part sarcomas. Although multiple translocation partners are fused to TFE3, each translocation product retains TFE3's basic helix-loop-helix leucine zipper. We have identified the genes fused by the chromosomal translocation t(6;11)(p21.1;q13), characteristic of another subset of renal neoplasms. In two primary tumors we found that Alpha, an intronless gene, rearranges with the first intron of TFEB, just upstream of TFEB's initiation ATG, preserving the entire TFEB coding sequence. Fluorescence in situ hybridization confirmed the involvement of both TFEB and Alpha in this translocation. Although the Alpha promoter drives expression of this fusion gene, the Alpha gene does not contribute to the ORF. Whereas TFE3 is typically fused to partner proteins in subsets of renal tumors, we found that wild-type, unfused TFE3 stimulates clonogenic growth in a cell-based assay, suggesting that dysregulated expression, rather than altered function of TFEB or TFE3 fusions, may confer neoplastic properties, a mechanism reminiscent of MYC activation by promoter substitution in Burkitt's lymphoma. Alpha-TFEB is thus identified as a fusion gene in a subset of pediatric renal neoplasms.M ITF, TFE3, TFEB, and TFEC are closely related basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factors (1-8) that may homo-or heterodimerize in all combinations to bind DNA (9). These factors share sequence homology in their DNA-contacting basic domains (10), as well as activation domains, and recognize identical DNA sequences (9), suggesting that they may regulate similar downstream targets. Genetic and biochemical studies have revealed functional overlap of MiT activity in certain developmental lineages. Specifically, use of knockout mice by Jenkins and colleagues (8) has elegantly demonstrated that, whereas mutation of either Mitf or TFE3 in mice does not disrupt osteoclast development, mutation of both genes or presence of a dominant-negative allele produces severe osteopetrosis. Homozygous mutation of MITF in the mouse is particularly devastating to the melanocyte lineage, resulting in failure of melanocyte development (5). In humans, Mitf haploinsufficiency results in type IIa Waardenburg syndrome (11). Mice homozygous null for TFE3 or TFEC had no recognized abnormalities (8), but TFEB nulls exhibited embryonic lethality associated with placental vascular defects (12). In addition, Mitf and TFE3 have been found to undergo identical modifications after cytokine stimulation (13), and MITF has been shown to directly regulate BCL2, a key apoptotic regulator, in a manner important for melanocyte and melanoma surv...

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Linkage of M-CSF Signaling to Mitf, TFE3, and the Osteoclast Defect in Mitfmi/mi Mice

Cited by 143 publications

References 52 publications

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

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

bcn-1 Element-dependent Activation of the Laminin γ1 Chain Gene by the Cooperative Action of Transcription Factor E3 (TFE3) and Smad Proteins

Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation

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