Structure and Evolution of the HumanSPRR3Gene: Implications for Function and Regulation

Fischer, David F.; Sark, M W; Lehtola, Marika M.; Gibbs, Susan; Putte, Pieter van de; Backendorf, Claude

doi:10.1006/geno.1998.5622

Cited by 36 publications

(27 citation statements)

References 61 publications

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“…In situ hybridization also demonstrates increased expression of ESE-1 in the granular layer, with little or no expression in the basal layers of the skin, suggesting a role for ESE-1 in terminal differentiation of keratinocytes (4,7). Expression of ESE-1 correlates with the upregulation of several terminal differentiation markers of the skin such as the small proline-rich proteins SPRR2A, SPRR1, and SPRR3 as well as transglutaminase 3 and profilaggrin (4,7,(23)(24)(25). The regulatory elements of each of these genes contain conserved binding sites for Ets factors that are critical for epithelium-and differentiation-specific gene expression (23)(24)(25)(26)(27)(28)(29).…”

Section: The Nucleotide Sequence(s) Reported In This Paper Has Been Smentioning

confidence: 95%

“…Expression of ESE-1 correlates with the upregulation of several terminal differentiation markers of the skin such as the small proline-rich proteins SPRR2A, SPRR1, and SPRR3 as well as transglutaminase 3 and profilaggrin (4,7,(23)(24)(25). The regulatory elements of each of these genes contain conserved binding sites for Ets factors that are critical for epithelium-and differentiation-specific gene expression (23)(24)(25)(26)(27)(28)(29). ESE-1, indeed, binds to and transactivates the promoters of the SPRR2A, SPRR1, SPRR3, transglutaminase 3, and profilaggrin genes, indicating that ESE-1 induced during terminal differentiation might regulate the expression of a whole set of terminal differentiation genes (4,7,(23)(24)(25).…”

Section: The Nucleotide Sequence(s) Reported In This Paper Has Been Smentioning

confidence: 99%

“…The regulatory elements of each of these genes contain conserved binding sites for Ets factors that are critical for epithelium-and differentiation-specific gene expression (23)(24)(25)(26)(27)(28)(29). ESE-1, indeed, binds to and transactivates the promoters of the SPRR2A, SPRR1, SPRR3, transglutaminase 3, and profilaggrin genes, indicating that ESE-1 induced during terminal differentiation might regulate the expression of a whole set of terminal differentiation genes (4,7,(23)(24)(25). The induction of the SPRR2A gene has recently been shown to involve, in addition to ESE-1, the ubiquitously expressed transcription factor AP-1 (23).…”

Section: The Nucleotide Sequence(s) Reported In This Paper Has Been Smentioning

confidence: 99%

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Characterization of ESE-2, a Novel ESE-1-related Ets Transcription Factor That Is Restricted to Glandular Epithelium and Differentiated Keratinocytes

Oettgen¹,

Kas²,

Dube³

et al. 1999

Journal of Biological Chemistry

118

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Epithelial cell differentiation is tightly controlled by distinct sets of transcription factors that regulate the expression of stage-specific genes. We recently isolated the first epithelium-specific Ets transcription factor (ESE-1). Here we describe the characterization of ESE-2, a second epithelium-restricted ESE-1-related Ets factor. Like ESE-1, ESE-2 is induced during keratinocyte differentiation. However, whereas ESE-1 is expressed in the majority of epithelial cell types, ESE-2 expression is restricted to differentiated keratinocytes and glandular epithelium such as salivary gland, prostate, mammary gland, and kidney. In contrast to ESE-1, full-length ESE-2 binds poorly to DNA due to the presence of a negative regulatory domain at the amino terminus. Furthermore, although ESE-1 and the amino-terminally deleted ESE-2 bind with similar affinity to the canonical E74 Ets site, ESE-2 and ESE-1 differ strikingly in their relative affinity toward binding sites in the c-MET and PSMA promoters. Similarly, ESE-1 and ESE-2 drastically differ in their ability to transactivate epitheliumspecific promoters. Thus, ESE-2, but not ESE-1, transactivates the parotid gland-specific PSP promoter and the prostate-specific PSA promoter. In contrast, ESE-1 transactivates the keratinocyte-specific SPRR2A promoter Ets site and the prostate-specific PSMA promoter significantly better than ESE-2. Our results demonstrate the existence of a unique class of related epitheliumspecific Ets factors with distinct functions in epithelial cell gene regulation.Normal epithelial cell development, proliferation, and differentiation are induced by mesenchymal-epithelial interactions and involve cell-cell interactions, extracellular matrix, and soluble growth and differentiation factors. These interactions trigger the activation or expression of a distinct set of transcription factors leading to a specific pattern of gene expression along a tightly controlled pathway. Abnormalities in this process due to deregulated gene expression can lead to the development of benign adenomas or malignant carcinomas that make up the majority of solid tumors. In order to understand tumor development, it is therefore critical to understand normal epithelial cell differentiation and proliferation. Whereas rapid progress in understanding immune system development and gene regulation has led to the discovery and characterization of a whole set of genes involved in leukemia and lymphoma development, relatively little is known about epithelial cell differentiation and organ development and the mechanisms involved in solid tumor formation. Most of the genes involved in chromosomal translocations in leukemias and lymphomas encode transcription factors that under normal physiological conditions coordinate the correct spatial and temporal expression of genes (1). We therefore postulate that similar mechanisms of oncogenesis play a role in epithelium-derived tumors as well. It is thus surprising that many aspects of epithelium-specific gene expression have not been explore...

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Section: The Nucleotide Sequence(s) Reported In This Paper Has Been Smentioning

confidence: 95%

Section: The Nucleotide Sequence(s) Reported In This Paper Has Been Smentioning

confidence: 99%

Section: The Nucleotide Sequence(s) Reported In This Paper Has Been Smentioning

confidence: 99%

See 1 more Smart Citation

Characterization of ESE-2, a Novel ESE-1-related Ets Transcription Factor That Is Restricted to Glandular Epithelium and Differentiated Keratinocytes

Oettgen¹,

Kas²,

Dube³

et al. 1999

Journal of Biological Chemistry

118

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“…62 In addition, the promoter region of the human SPRR3 gene contains multiple regulatory elements involved in keratinocyte differentiation-specific expression, including a high-affinity ETS binding site bound by ESE-1. 63 Collectively, the findings obtained from the aforementioned studies suggest that ESE-1 plays an important role in regulating terminal differentiation of the epidermal epithelium; however, further studies are required to understand the exact role of ESE-1 in this important physiological process.…”

Section: Ese-1 In Terminal Differentiation Of the Epidermal Skin Epitmentioning

confidence: 99%

Multiple roles of the epithelium-specific ETS transcription factor, ESE-1, in development and disease

Oliver

Kushwah

2012

Laboratory Investigation

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The E26 transformation-specific (ETS) family of transcription factors comprises of 27 and 26 members in humans and mice, respectively, which are known to regulate many different biological processes, including cell proliferation, cell differentiation, embryonic development, neoplasia, hematopoiesis, angiogenesis, and inflammation. The epitheliumspecific ETS transcription factor-1 (ESE-1) is a physiologically important ETS transcription factor, which has been shown to play a role in the pathogenesis of various diseases, and was originally characterized as having an epithelial-restricted expression pattern, thus placing it within the epithelium-specific ETS subfamily. Despite a large body of published work on ETS biology, much remains to be learned about the precise functions of ESE-1 and other epithelium-specific ETS factors in regulating diverse disease processes. Clues as to the specific function of ESE-1 in the setting of various diseases can be obtained from studies aimed at examining the expression of putative target genes regulated by ESE-1. Thus, this review will focus primarily on the various roles of ESE-1 in different pathophysiological processes, including regulation of epithelial cell differentiation during both intestinal development and lung regeneration; regulation of dendritic cell-driven T-cell differentiation during allergic airway inflammation; regulation of mammary gland development and breast cancer; and regulation of the effects of inflammatory stimuli within the setting of synovial joint and vascular inflammation. Understanding the exact mechanisms by which ESE-1 regulates these processes can have important implications for the treatment of a wide range of diseases. KEYWORDS: cancer; development; epithelial cell differentiation; ESE-1; ETS transcription factor; inflammation; regeneration The E26 transformation-specific (ETS) family of transcription factors is characterized by a highly conserved 84-aminoacid DNA-binding domain, known as the ETS domain. 1 Because the first member of the ETS family, the v-ets oncogene, was originally discovered as part of a fusion protein with gag and myb expressed by the E26 avian erythroblastosis-transforming retrovirus and its DNA-binding domain is E26 transformation-specific, this 84-amino-acid DNA-binding domain was named the ETS domain. 1 The ETS domain is usually located within the carboxyl-terminal region of the protein as a winged helix-turn-helix structural motif and mediates binding to sites of purine-rich DNA, commonly containing a core consensus sequence of GGAA/T, within the promoter and enhancer regions of target genes. 2,3 Many ETS transcription factors also contain a pointed domain, which is located within the amino-terminal region and is involved in protein-protein interactions. 2 Approximately 30 members of the ETS transcription factor family have been identified in mammals (ie 27 in humans and 26 in mice), 4 and have been shown to play crucial roles in the regulation of many physiological and pathological processes, such as embryonic develo...

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“…However, Fra-1, JunB and JunD appear to be responsible for the regulation of involucrin promoter activity by phorbol esters . Functional synergism between AP-1 and ETS proteins was found to mediate expression of the keratinocyte terminal di erentiation markers small proline-rich protein (SPRR)-1A (Sark et al, 1998) and SPRR3 (Fischer et al, 1999). In contrast, expression of another member of the SPRR family sprr2, is negatively regulated by c-Jun.…”

Section: Regulation and Function Of Fos And Jun Proteins In Keratinocmentioning

confidence: 99%

Function and regulation of AP-1 subunits in skin physiology and pathology

2001

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The mouse skin has become the model of choice to study the regulation and function of AP-1 subunits in many physiological and pathological processes in vivo and in vitro. Genetically modi®ed mice, in vitro reconstituted skin equivalents and epidermal cell lines were established, in which AP-1-regulated genetic programs of cell proliferation, di erentiation and tumorigenesis can be analysed. Since the epidermis, as our interface with the environment, is subjected to radiation and injury, signal transduction pathways and critical AP-1 members regulating the mammalian stress response could be identi®ed. Regulated expression of important components of the cytokine network, cell surface receptors and proteases, which orchestrate the process of wound healing has been found to rely on AP-1 activity. Here we review our current knowledge on the function of AP-1 subunits and AP-1 target genes in these fascinating ®elds of skin physiology and pathology. Oncogene (2001) 20, 2413 ± 2423.

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Structure and Evolution of the HumanSPRR3Gene: Implications for Function and Regulation

Cited by 36 publications

References 61 publications

Characterization of ESE-2, a Novel ESE-1-related Ets Transcription Factor That Is Restricted to Glandular Epithelium and Differentiated Keratinocytes

Characterization of ESE-2, a Novel ESE-1-related Ets Transcription Factor That Is Restricted to Glandular Epithelium and Differentiated Keratinocytes

Multiple roles of the epithelium-specific ETS transcription factor, ESE-1, in development and disease

Function and regulation of AP-1 subunits in skin physiology and pathology

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