ETS-related transcription factor Elf-4

Definition:

Transcriptional activator that binds to DNA sequences containing the consensus 5'-WGGA-3'. Transactivates promoters of the hematopoietic growth factor genes CSF2, IL3, IL8, and of the bovine lysozyme gene. Acts synergistically with RUNX1 to transactivate the IL3 promoter (By similarity). Transactivates the PRF1 promoter in natural killer (NK) cells and CD8+ T cells. Plays a role in the development and function of NK and NK T-cells and in innate immunity. Controls the proliferation and homing of CD8+ T-cells via the Kruppel-like factors KLF4 and KLF2 (By similarity). Controls cell senescence in a p53-dependent manner. Can also promote cellular transformation through inhibition of the p16 pathway. Is a transcriptional regulator of inflammation, controlling T-helper 17 (Th17) cells and macrophage inflammatory responses. Required for sustained transcription of anti-inflammatory genes, including IL1RN. Is a negative regulator of pro-inflammatory cytokines expression including IL17A, IL1B, IL6, TNFA and CXCL1. Down-regulates expression of TREM1, a cell surface receptor involved in the amplification of inflammatory responses (By similarity).

References:

[1]. Paul M Tyler, et al. Human autoinflammatory disease reveals ELF4 as a transcriptional regulator of inflammation. Nat Immunol. 2021 Sep;22(9):1118-1126. [Content Brief]

[2]. Gan Sun, et al. Loss of Function Mutation in ELF4 Causes Autoinflammatory and Immunodeficiency Disease in Human. J Clin Immunol. 2022 May;42(4):798-810. [Content Brief]

[3]. Cyrus V Hedvat, et al. Myeloid ELF1-like factor is a potent activator of interleukin-8 expression in hematopoietic cells. J Biol Chem. 2004 Feb 20;279(8):6395-400. [Content Brief]

[4]. Goro Sashida, et al. ELF4/MEF activates MDM2 expression and blocks oncogene-induced p16 activation to promote transformation. Mol Cell Biol. 2009 Jul;29(13):3687-99. [Content Brief]

[5]. Y Miyazaki, et al. MEF, a novel transcription factor with an Elf-1 like DNA binding domain but distinct transcriptional activating properties. Oncogene. 1996 Oct 17;13(8):1721-9. [Content Brief]

[6]. D N Aryee, et al. Cloning of a novel human ELF-1-related ETS transcription factor, ELFR, its characterization and chromosomal assignment relative to ELF-1. Gene. 1998 Mar 27;210(1):71-8. [Content Brief]

[7]. S Mao, et al. Functional and physical interactions between AML1 proteins and an ETS protein, MEF: implications for the pathogenesis of t(8;21)-positive leukemias. Mol Cell Biol. 1999 May;19(5):3635-44. [Content Brief]

[8]. Mary Ann Suico, et al. Myeloid Elf-1-like factor, an ETS transcription factor, up-regulates lysozyme transcription in epithelial cells through interaction with promyelocytic leukemia protein. J Biol Chem. 2004 Apr 30;279(18):19091-8. [Content Brief]

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