Role of Ets Proteins in Development, Differentiation, and Function of T‐Cell Subsets

Liu, Mian; Gao, Weiying; Velkinburgh, Jennifer C. van; Wu, Yuzhang; Ni, Bing; Tian, Yi

doi:10.1002/med.21361

Cited by 17 publications

(25 citation statements)

References 219 publications

(335 reference statements)

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“…The founding member of the ETS transcription family ETS-1 shows extensive sequence conservation among vertebrates and alongside its sibling ETS-2 has critical roles in the development of the heart and circulatory system [ 25 , 26 , 27 ]. In adult humans, mice and chickens, ETS-1 expression is particularly localized to immune tissues (e.g., thymus, spleen and lymph nodes in mice), consistent with roles in regulating B cell, T cell and NK cell differentiation, whereas ETS-2 expression is more widespread [ 11 , 25 , 28 ].…”

Section: Ets-1 Ets-2 and The Constitutive Photomorphogenesis 1 (Cop1) Complexmentioning

confidence: 94%

“…The majority of ETS proteins are phosphorylation targets of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinases (ERKs), C-JUN N-terminal kinases (JNKs) and p38 kinases [ 8 ]. Several are key ERK responders, and as such are involved in the regulation of a diverse portfolio of cellular processes including proliferation, differentiation and survival [ 9 , 10 , 11 ]. As such, dysregulated expression and activities of ETS family members are frequently reported in cancers, with oncogenic fusions also prevalent [ 5 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development

Ducker

Shaw

2021

IJMS

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Genome expansion, whole genome and gene duplication events during metazoan evolution produced an extensive family of ETS genes whose members express transcription factors with a conserved winged helix-turn-helix DNA-binding domain. Unravelling their biological roles has proved challenging with functional redundancy manifest in overlapping expression patterns, a common consensus DNA-binding motif and responsiveness to mitogen-activated protein kinase signalling. Key determinants of the cellular repertoire of ETS proteins are their stability and turnover, controlled largely by the actions of selective E3 ubiquitin ligases and deubiquitinases. Here we discuss the known relationships between ETS proteins and enzymes that determine their ubiquitin status, their integration with other developmental signal transduction pathways and how suppression of ETS protein ubiquitination contributes to the malignant cell phenotype in multiple cancers.

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Section: Ets-1 Ets-2 and The Constitutive Photomorphogenesis 1 (Cop1) Complexmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development

Ducker

Shaw

2021

IJMS

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“…Etv6 acts predominantly as a transcriptional repressor and is antagonized by other PNT-containing ETS proteins. In particular, reciprocal expression and functional antagonism of Etv6 and Ets1 have been reported in Drosophila melanogaster development for the respective orthologues Yan and Pointed (Graham et al, 2010; Boisclair Lachance et al, 2014) and in the differentiation of CD4 + effector T cells (Liu et al, 2016). Etv6 is prominently expressed in hematopoietic stem and progenitor cells (HSPCs) and is essential for HSPC maintenance and thrombopoiesis (Hock et al, 2004; Hock and Shimamura, 2017).…”

Section: Introductionmentioning

confidence: 99%

Transcription factor Etv6 regulates functional differentiation of cross-presenting classical dendritic cells

Lau

Tiniakou

Perez

et al. 2018

Journal of Experimental Medicine

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An IRF8-dependent subset of conventional dendritic cells (cDCs), termed cDC1, effectively cross-primes CD8 T cells and facilitates tumor-specific T cell responses. Etv6 is an ETS family transcription factor that controls hematopoietic stem and progenitor cell (HSPC) function and thrombopoiesis. We report that like HSPCs, cDCs express Etv6, but not its antagonist, ETS1, whereas interferon-producing plasmacytoid dendritic cells (pDCs) express both factors. Deletion of Etv6 in the bone marrow impaired the generation of cDC1-like cells in vitro and abolished the expression of signature marker CD8α on cDC1 in vivo. Moreover, Etv6-deficient primary cDC1 showed a partial reduction of cDC-specific and cDC1-specific gene expression and chromatin signatures and an aberrant up-regulation of pDC-specific signatures. Accordingly, DC-specific Etv6 deletion impaired CD8 T cell cross-priming and the generation of tumor antigen-specific CD8 T cells. Thus, Etv6 optimizes the resolution of cDC1 and pDC expression programs and the functional fitness of cDC1, thereby facilitating T cell cross-priming and tumor-specific responses.

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“…Unsurprisingly, many ETS transcription factors are implicated in the emergence and progression of cancer ( Seth and Watson, 2005 ; Kar and Gutierrez-Hartmann, 2013 ). Aside from their roles in malignancy, the ETS factors are also involved in cellular homoeostasis and immune regulation ( Gallant and Gilkeson, 2006 ; Garrett-Sinha, 2013 ; Liu et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Roles and regulations of the ETS transcription factor ELF4/MEF

2016

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Most E26 transformation-specific (ETS) transcription factors are involved in the pathogenesis and progression of cancer. This is in part due to the roles of ETS transcription factors in basic biological processes such as growth, proliferation, and differentiation, and also because of their regulatory functions that have physiological relevance in tumorigenesis, immunity, and basal cellular homoeostasis. A member of the E74-like factor (ELF) subfamily of the ETS transcription factor family—myeloid elf-1-like factor (MEF), designated as ELF4—has been shown to be critically involved in immune response and signalling, osteogenesis, adipogenesis, cancer, and stem cell quiescence. ELF4 carries out these functions as a transcriptional activator or through interactions with its partner proteins. Mutations in ELF4 cause aberrant interactions and induce downstream processes that may lead to diseased cells. Knowing how ELF4 impinges on certain cellular processes and how it is regulated in the cells can lead to a better understanding of the physiological and pathological consequences of modulated ELF4 activity.

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Role of Ets Proteins in Development, Differentiation, and Function of T‐Cell Subsets

Cited by 17 publications

References 219 publications

Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development

Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development

Transcription factor Etv6 regulates functional differentiation of cross-presenting classical dendritic cells

Roles and regulations of the ETS transcription factor ELF4/MEF

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