Genetic and Physical Interactions betweenMicrophthalmia Transcription Factor and PU.1 Are Necessary for Osteoclast Gene Expression and Differentiation

Luchin, A; Suchting, Steven; Merson, Tobias D.; Rosol, Thomas J.; Hume, David; Cassady, A. I.; Ostrowski, Michael C.

doi:10.1074/jbc.m106418200

Cited by 107 publications

(91 citation statements)

References 40 publications

(37 reference statements)

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“…Mice heterozygous for both the mutant Mi allele and a PU.1 null allele also develop osteopetrosis. The size and number of osteoclasts were not altered in the double heterozygous mutant mice, indicating that the defect lies in mature osteoclast function [41]. The critical molecules regulating osteoclast differentiation and function are summarized in Fig.…”

Section: Molecular Control Of Osteoclast Differentiationmentioning

confidence: 99%

“…Moreover, interleukin-1 (IL-1) activates osteoclast-specific genes including TRAP and OSCAR, in part, via the MITF pathway [61]. Mi mutant osteoclasts are primarily mononuclear and express decreased levels of TRAP [41,62]. Mice heterozygous for both the mutant Mi allele and a PU.1 null allele also develop osteopetrosis.…”

Section: Molecular Control Of Osteoclast Differentiationmentioning

confidence: 99%

“…In addition, PU.1 and microphthalmia-associated transcription factor MITF, a basic helix-loop-helix-leucine zipper protein, collaborate to increase an expression of target genes like cathepsin K (Ctsk) and acid phosphatase 5 (Acp5) during osteoclast differentiation [41,42]. They recruit p38 mitogen activated protein kinase and Nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) to target genes during osteoclast differentiation [43].…”

Section: Molecular Control Of Osteoclast Differentiationmentioning

confidence: 99%

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Molecular Understanding of Osteoclast Differentiation and Physiology

Lee

2010

Endocrinol Metab

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Section: Molecular Control Of Osteoclast Differentiationmentioning

confidence: 99%

Section: Molecular Control Of Osteoclast Differentiationmentioning

confidence: 99%

Section: Molecular Control Of Osteoclast Differentiationmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Understanding of Osteoclast Differentiation and Physiology

Lee

2010

Endocrinol Metab

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“…Using candidate approaches, multiple pigmentation-associated factors have been thus recognized, although it is noteworthy that factors other than MITF are undoubtedly important in their regulation as well, because the endogenous genes are not always predictably up-or down-regulated by modulation of Mitf expression alone (Gaggioli et al 2003). Other transcription factors of importance in the regulation of potential Mitf targets include CREB/ATF1, SOX10 (Jiao et al 2004;Ludwig et al 2004), Pax3 (as a negative regulator and potential media-tor of melanocyte stem cell maintenance) (Lang et al 2005), OTX2 in retinal pigment epithelium (MartinezMorales et al 2003), CBP and MAZR (in mast cells) (Ogihara et al 1999;Morii et al 2002), Pu.1 in osteoclast target genes Luchin et al 2001;Cassady et al 2003;So et al 2003;Partington et al 2004), Wnt/ LEF (Yasumoto et al 2002), and probably others as well.…”

Section: Transcriptional Targets Of Mitfmentioning

confidence: 99%

Malignant melanoma: genetics and therapeutics in the genomic era

2006

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Cell for cell, probably no human cancer is as aggressive as melanoma. It is among a handful of cancers whose dimensions are reported in millimeters. Tumor thickness approaching 4 mm presents a high risk of metastasis, and a diagnosis of metastatic melanoma carries with it an abysmal median survival of 6-9 mo. What features of this malignancy account for such aggressive behavior? Is it the migratory history of its cell of origin or the programmed adaptation of its differentiated progeny to environmental stress, particularly ultraviolet radiation? While the answers to these questions are far from complete, major strides have been made in our understanding of the cellular, molecular, and genetic underpinnings of melanoma. More importantly, these discoveries carry profound implications for the development of therapies focused directly at the molecular engines driving melanoma, suggesting that we may have reached the brink of an unprecedented opportunity to translate basic science into clinical advances. In this review, we attempt to summarize our current understanding of the genetics and biology of this disease, drawing from expanding genomic information and lessons from development and genetically engineered mouse models. In addition, we look forward toward how these new insights will impact on therapeutic options for metastatic melanoma in the near future. The diseaseMelanomas most often arise within epidermal melanocytes of the skin, although they can also derive from noncutaneous melanocytes such as those lining the choroidal layer of the eye, GI and GU mucosal surfaces, or the meninges. Melanoma is also among the more common causes of "metastatic cancer of unknown primary," which may reflect either a propensity to arise in unexpected sites along the neural crest migratory route, or rapid growth of poorly differentiated lesions arising from indolent or unrecognized cutaneous primary lesions. Clinical staging for primary cutaneous melanoma employs measurements of thickness (in millimeters), presence of ulceration, penetration through cutaneous layers, mitotic rate, evidence of "in transit" metastasis, tumor spread to draining lymph nodes, and evidence of distant metastasis. Management issues in melanoma can be classified in terms of prevention, diagnosis, local disease management, and treatment of metastatic disease.In view of the epidemiological and emerging experimental evidence linking melanoma incidence to UV exposure and skin phototype, prevention and screening strategies represent key areas for reduction of disease incidence and severity. For most cutaneous melanomas in the so-called radial growth phase (e.g., thin melanomas), surgical removal affords curative treatment. In contrast, a significant fraction of patients diagnosed with intermediate-thickness (2-4 mm) cutaneous melanoma eventually succumb to recurrence at regional or distant sites.Critical biological questions facing the melanoma research community include: (1) What genetic and environmental factors contribute to and/or modulate risk of melanom...

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“…Similarly, a number of protein partners have been identified for PU.1, but complexes in mast cells have not been reported. Intriguingly, however, Mitf and c-Jun, transcription factors abundantly expressed in mast cells, have been shown to bind with PU.1 (102)(103)(104), however the biological functions mediated by these interactions in mast cells in unknown.…”

Section: Mechanisms Of Transcription Factor Cooperationmentioning

confidence: 99%

Mast cell transcriptional networks

Takemoto

Lee

Jegga

et al. 2008

Blood Cells, Molecules, and Diseases

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Unregulated activation of mast cells can contribute to the pathogenesis of inflammatory and allergic diseases, including asthma, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis (1;2). Absence of mast cells in animal models can lead to impairment in the innate immune response to parasites and bacterial infections (3)(4)(5). Aberrant clonal accumulation and proliferation of mast cells can result in a variety of diseases ranging from benign cutaneous mastocytosis to systemic mastocytosis or mast cell leukemia(6). Understanding mast cell differentiation provides important insights into mechanisms of lineage selection during hematopoiesis and can provide targets for new drug development to treat mast cell disorders,. In this review, we discuss controversies related to development, sites of origin,, and the transcriptional program of mast cells. KeywordsMast cells; transcription factors; GATA; PU.1; Mitf Origins of Mast CellsLike other granulocytes (neutrophils, eosinophils and basophils), mast cells are derived from hematopoietic stem cells in the marrow; however, they are unique with regard to the tissue compartments in which they traffic and reside. The gastrointestinal mucosa is the major compartment occupied by committed mast cell precursors in the mouse (7). Trafficking to these compartments is dependent on the expression of the alpha4 beta7 integrin and the chemokine receptor CXCR2.(8;9) Mast cell progenitors migrate to the connective tissue of the skin, lung, and the mucosa of other gastrointestinal tissues where they mature under the influence local Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Transplantation studies in mice indicate that mast cells are derived from hematopoietic stem cells of marrow (or spleen)(10;11). Studies using prospectively identified hematopoietic precursors have reported different precursor cells that give rise to the committed mast cell progenitor One study found that the committed mast cell progenitor (MCP) arose from an early multipotential progenitor (MPP) that is distinct from the common myeloid progenitor (12). However, using a similar strategy to prospectively isolate hematopoietic precursors from mouse marrow, another study found that the MCP was derived from either the common myeloid progenitor or the granulocyte-monocyte progenitor(13) (Figure 1). Plasticity may permit other committed progenitor cell populations to be "reprogrammed" into the mast cell lineage by altering the expression of selected transcription factors. Isolated common lymphoid precursors that are retrovirally-tranduced with the tr...

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Genetic and Physical Interactions betweenMicrophthalmia Transcription Factor and PU.1 Are Necessary for Osteoclast Gene Expression and Differentiation

Cited by 107 publications

References 40 publications

Molecular Understanding of Osteoclast Differentiation and Physiology

Molecular Understanding of Osteoclast Differentiation and Physiology

Malignant melanoma: genetics and therapeutics in the genomic era

Mast cell transcriptional networks

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