Activating transcription factor 4 (tax-responsive enhancer element B67), also known as ATF4, is a protein that in humans is encoded by the ATF4 gene. [5] [6]
Activating transcription factor 4 (tax-responsive enhancer element B67), also known as ATF4, is a protein that in humans is encoded by the ATF4 gene. [5] [6]
This gene encodes a transcription factor that was originally identified as a widely expressed mammalian DNA binding protein that could bind a tax-responsive enhancer element in the LTR of HTLV-1. The encoded protein was also isolated and characterized as the cAMP-response element binding protein 2 (CREB-2). ATF4 is not a functional transcription factor by itself but one-half of many possible heterodimeric transcription factors. Because ATF4 can simultaneously participate in multiple distinct heterodimers, the overall set of genes that require ATF4 for maximal expression in a specific context (ATF4-dependent genes) can be a mixture of genes that are regulated by different ATF4 heterodimers, with some ATF4-dependent genes activated by one ATF4 heterodimer and other ATF4-dependent genes activated by other ATF4 heterodimers. [7]
The protein encoded by this gene belongs to a family of DNA-binding proteins that includes the AP-1 family of transcription factors, cAMP-response element binding proteins (CREBs) and CREB-like proteins. These transcription factors share a leucine zipper region that is involved in protein–protein interactions, located C-terminal to a stretch of basic amino acids that functions as a DNA-binding domain. Two alternative transcripts encoding the same protein have been described. Two pseudogenes are located on the X chromosome at q28 in a region containing a large inverted duplication. [8]
ATF4 transcription factor is also known to play role in osteoblast differentiation along with RUNX2 and osterix. [9] Terminal osteoblast differentiation, represented by matrix mineralization, is significantly inhibited by the inactivation of JNK. JNK inactivation downregulates expression of ATF-4 and, subsequently, matrix mineralization. [10] IMPACT protein regulates ATF4 in C. elegans to promote lifespan. [11]
ATF4 is also involved in the cannabinoid Δ9-tetrahydrocannabinol–induced apoptosis in cancer cells, by the proapoptotic role of the stress protein p8 via its upregulation of the endoplasmic reticulum stress-related genes ATF4, CHOP, and TRB3. [12] [13]
The translation of ATF4 is dependent on upstream open reading frames located in the 5'UTR. [14] The location of the second uORF, aptly named uORF2, overlaps with the ATF4 open-reading frame. During normal conditions, the uORF1 is translated, and then translation of uORF2 occurs only after eIF2-TC has been reacquired. Translation of the uORF2 requires that the ribosomes pass by the ATF4 ORF, whose start codon is located within uORF2. This leads to its repression. However, during stress conditions, the 40S ribosome will bypass uORF2 because of a decrease in concentration of eIF2-TC, which means the ribosome does not acquire one in time to translate uORF2. Instead ATF4 is translated. [14]
CREB-TF is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB was first described in 1987 as a cAMP-responsive transcription factor regulating the somatostatin gene.
Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the FOS gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV. It is a part of a bigger Fos family of transcription factors which includes c-Fos, FosB, Fra-1 and Fra-2. It has been mapped to chromosome region 14q21→q31. c-Fos encodes a 62 kDa protein, which forms heterodimer with c-jun, resulting in the formation of AP-1 complex which binds DNA at AP-1 specific sites at the promoter and enhancer regions of target genes and converts extracellular signals into changes of gene expression. It plays an important role in many cellular functions and has been found to be overexpressed in a variety of cancers.
P300/CBP-associated factor (PCAF), also known as K(lysine) acetyltransferase 2B (KAT2B), is a human gene and transcriptional coactivator associated with p53.
Activating transcription factor, ATF, is a group of bZIP transcription factors, which act as homodimers or heterodimers with a range of other bZIP factors. First, they have been described as members of the CREB/ATF family, whereas it turned out later that some of them might be more similar to AP-1-like factors such as c-Jun or c-Fos. In general, ATFs are known to respond to extracellular signals and this suggests an important role that they have in maintaining homeostasis. Some of these ATFs, such as ATF3, ATF4, and ATF6 are known to play a role in stress responses. Another example of ATFs function would be ATFx that can suppress apoptosis.
CAMP responsive element binding protein 1, also known as CREB-1, is a protein that in humans is encoded by the CREB1 gene. This protein binds the cAMP response element, a DNA nucleotide sequence present in many viral and cellular promoters. The binding of CREB1 stimulates transcription.
Cyclic AMP-dependent transcription factor ATF-3 is a protein that, in humans, is encoded by the ATF3 gene.
Cyclic AMP-dependent transcription factor ATF-1 is a protein that in humans is encoded by the ATF1 gene.
Activating transcription factor 6, also known as ATF6, is a protein that, in humans, is encoded by the ATF6 gene and is involved in the unfolded protein response.
GA-binding protein alpha chain is a protein that in humans is encoded by the GABPA gene.
Activating transcription factor 2, also known as ATF2, is a protein that, in humans, is encoded by the ATF2 gene.
cAMP responsive element modulator is a protein that in humans is encoded by the CREM gene, and it belongs to the cAMP-responsive element binding protein family. It has multiple isoforms, which act either as repressors or activators. CREB family is important for in regulating transcription in response to various stresses, metabolic and developmental signals. CREM transcription factors also play an important role in many physiological systems, such as cardiac function, circadian rhythms, locomotion and spermatogenesis.
Transcription factor MafG is a bZip Maf transcription factor protein that in humans is encoded by the MAFG gene.
Cyclic AMP-responsive element-binding protein 3 is a protein that in humans is encoded by the CREB3 gene.
Activating transcription factor 5, also known as ATF5, is a protein that, in humans, is encoded by the ATF5 gene.
CAMP responsive element binding protein-like 1, also known as CREBL1, is a protein which in humans is encoded by the CREBL1 gene.
Cyclic AMP-dependent transcription factor ATF-7 is a protein that in humans is encoded by the ATF7 gene.
DNA-binding protein RFX2 is a protein that in humans is encoded by the RFX2 gene.
Transcription factor RFX3 is a protein that in humans is encoded by the RFX3 gene.
The Basic Leucine Zipper Domain is found in many DNA binding eukaryotic proteins. One part of the domain contains a region that mediates sequence specific DNA binding properties and the leucine zipper that is required to hold together (dimerize) two DNA binding regions. The DNA binding region comprises a number of basic amino acids such as arginine and lysine. Proteins containing this domain are transcription factors.
CREB/ATF bZIP transcription factor is a protein that in humans is encoded by the CREBZF gene.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
PDB gallery | |
|---|---|
|
