Transcription factor E74 like ETS transcription factor 4(ELF4),a member of the ETS family,is highly expressed in normal human hematopoietic tissue,ovary,placenta,colon,and certain pathological cell lines.During normal...Transcription factor E74 like ETS transcription factor 4(ELF4),a member of the ETS family,is highly expressed in normal human hematopoietic tissue,ovary,placenta,colon,and certain pathological cell lines.During normal physiological processes,ELF4 regulates differentiation in osteogenic,adipocyte,and neuronal types.It also exerts a critical impact on the development of the immune system.However,its function is dysregulated through posttranslational modifications,gene fusions,and complex signaling crosstalk under pathological conditions.Furthermore,serving as a double-edged sword in cancer,ELF4 exhibits both tumorsuppressing and tumor-promoting effects.Specifically,ELF4 plays a critical role in cancer metastasis,proliferation,and modulation of the tumor microenvironment.This review provides an in-depth overview of the molecular structure and post-translational modifications of ELF4.It also summarizes the hallmarks of ELF4 in physiology and diseases,with a particular focus on its significance in oncology.Notably,this review underscores the potential of ELF4 as a prognostic biomarker,highlighting its clinical relevance.Finally,it discusses unresolved questions and future research directions of ELF4.An in-depth understanding of ELF4 biology could facilitate its clinical translation and offer promising targeted therapeutic strategies.展开更多
Background ELF4 deficiency has been recently recognized as a novel disorder within the spectrum of inborn errors of immunity(IEIs),specifically categorized as a“disease of immune dysregulation.”Cases of this conditi...Background ELF4 deficiency has been recently recognized as a novel disorder within the spectrum of inborn errors of immunity(IEIs),specifically categorized as a“disease of immune dysregulation.”Cases of this condition,reported by our team and others,are very limited worldwide.As such,our current knowledge of this new disease remains preliminary.This review aims to provide a brief overview of the clinical manifestations,pathogenesis,and treatment strategies for this novel IEI.Data sources A comprehensive review was conducted after an extensive literature search in the PubMed/Medline database and websites concerning transcriptional factor ELF4 and reports concerning patients with ELF4 deficiency.Our search strategy was“ELF4 OR ETS-related transcription factor Elf-4 OR EL4-like factor 4 OR myeloid Elf-1-like factor”as of the time of manuscript submission.Results The current signature manifestations of ELF4 deficiency disorder are recurrent and prolonged oral ulcer,abdominal pain,and diarrhea in pediatric males.In some cases,immunodeficiency and autoimmunity can also be prominent.Targeted Sanger sequencing or whole exome sequencing can be used to detect variation in ELF4 gene.Western blotting for ELF4 expression of the patient’s cells can confirm the pathogenic effect of the variant.To fully confirm the pathogenicity of the variant,further functional test is strongly advised.Glucocorticoid and biologics are the mainstream management of ELF4 deficiency disorder.Conclusions Pediatric males presenting with recurring ulcerations in digestive tract epithelium with or without recurrent fever should be suspected of DEX.When atypical presentations are prominent,variations in ELF4 gene should be carefully evaluated functionally due to the complex nature of ELF4 function.Experience of treating DEX includes use of glucocorticoid and biologics and more precise treatment needs more patients to identify and further mechanistic study.展开更多
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 su...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 E74-1ike factor （ELF） subfamily of the ETS transcription factor family--myeloid elf-l-Uke factor （MEF）, designated as ELF4~has been shown to be critically involved in immune response and signalling, osteogenesis, adipo- genesis, 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 dis- eased 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.展开更多
基金funded by the National Natural Science Foundation of China(No.U23A20451,82273310,82372917,82173313)the Natural Science Foundation of Hubei Province,China(No.2022CFA016)the Basic Research Support Program of Huazhong University of Science and Technology(China)(No.2023BR038).
文摘Transcription factor E74 like ETS transcription factor 4(ELF4),a member of the ETS family,is highly expressed in normal human hematopoietic tissue,ovary,placenta,colon,and certain pathological cell lines.During normal physiological processes,ELF4 regulates differentiation in osteogenic,adipocyte,and neuronal types.It also exerts a critical impact on the development of the immune system.However,its function is dysregulated through posttranslational modifications,gene fusions,and complex signaling crosstalk under pathological conditions.Furthermore,serving as a double-edged sword in cancer,ELF4 exhibits both tumorsuppressing and tumor-promoting effects.Specifically,ELF4 plays a critical role in cancer metastasis,proliferation,and modulation of the tumor microenvironment.This review provides an in-depth overview of the molecular structure and post-translational modifications of ELF4.It also summarizes the hallmarks of ELF4 in physiology and diseases,with a particular focus on its significance in oncology.Notably,this review underscores the potential of ELF4 as a prognostic biomarker,highlighting its clinical relevance.Finally,it discusses unresolved questions and future research directions of ELF4.An in-depth understanding of ELF4 biology could facilitate its clinical translation and offer promising targeted therapeutic strategies.
基金funded by National Natural Science Foundation of China(82101908,82371823)Postdoc Fund of Chongqing Natural Science Foundation(cstc2021jcyj-bshX0226).
文摘Background ELF4 deficiency has been recently recognized as a novel disorder within the spectrum of inborn errors of immunity(IEIs),specifically categorized as a“disease of immune dysregulation.”Cases of this condition,reported by our team and others,are very limited worldwide.As such,our current knowledge of this new disease remains preliminary.This review aims to provide a brief overview of the clinical manifestations,pathogenesis,and treatment strategies for this novel IEI.Data sources A comprehensive review was conducted after an extensive literature search in the PubMed/Medline database and websites concerning transcriptional factor ELF4 and reports concerning patients with ELF4 deficiency.Our search strategy was“ELF4 OR ETS-related transcription factor Elf-4 OR EL4-like factor 4 OR myeloid Elf-1-like factor”as of the time of manuscript submission.Results The current signature manifestations of ELF4 deficiency disorder are recurrent and prolonged oral ulcer,abdominal pain,and diarrhea in pediatric males.In some cases,immunodeficiency and autoimmunity can also be prominent.Targeted Sanger sequencing or whole exome sequencing can be used to detect variation in ELF4 gene.Western blotting for ELF4 expression of the patient’s cells can confirm the pathogenic effect of the variant.To fully confirm the pathogenicity of the variant,further functional test is strongly advised.Glucocorticoid and biologics are the mainstream management of ELF4 deficiency disorder.Conclusions Pediatric males presenting with recurring ulcerations in digestive tract epithelium with or without recurrent fever should be suspected of DEX.When atypical presentations are prominent,variations in ELF4 gene should be carefully evaluated functionally due to the complex nature of ELF4 function.Experience of treating DEX includes use of glucocorticoid and biologics and more precise treatment needs more patients to identify and further mechanistic study.
文摘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 E74-1ike factor （ELF） subfamily of the ETS transcription factor family--myeloid elf-l-Uke factor （MEF）, designated as ELF4~has been shown to be critically involved in immune response and signalling, osteogenesis, adipo- genesis, 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 dis- eased 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.
