ATF4

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
ATF4
Protein ATF4 PDB 1ci6.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesATF4, CREB-2, CREB2, TAXREB67, TXREB, activating transcription factor 4
External IDsMGI: 88096 HomoloGene: 1266 GeneCards: ATF4
Gene location (Human)
Chromosome 22 (human)
Chr.Chromosome 22 (human)[1]
Chromosome 22 (human)
Genomic location for ATF4
Genomic location for ATF4
Band22q13.1Start39,519,695 bp[1]
End39,522,685 bp[1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_182810
NM_001675

NM_001287180
NM_009716

RefSeq (protein)

NP_001666
NP_877962
NP_001666.2
NP_877962.1

NP_001274109
NP_033846

Location (UCSC)Chr 22: 39.52 – 39.52 MbChr 15: 80.26 – 80.26 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Function[edit]

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). 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.[7]

ATF4 transcription factor is also known to play role in osteoblast differentiation along with RUNX2 and osterix.[8] 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.[9] IMPACT protein regulates ATF4 in C. elegans to promote lifespan.[10]

Translation[edit]

The translation of ATF4 is dependent on upstream open reading frames located in the 5'UTR.[11] 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.[11]

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000128272 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000042406 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ Tsujimoto A, Nyunoya H, Morita T, Sato T, Shimotohno K (March 1991). "Isolation of cDNAs for DNA-binding proteins which specifically bind to a tax-responsive enhancer element in the long terminal repeat of human T-cell leukemia virus type I". Journal of Virology. 65 (3): 1420–6. PMC 239921. PMID 1847461.
  6. ^ Karpinski BA, Morle GD, Huggenvik J, Uhler MD, Leiden JM (June 1992). "Molecular cloning of human CREB-2: an ATF/CREB transcription factor that can negatively regulate transcription from the cAMP response element". Proceedings of the National Academy of Sciences of the United States of America. 89 (11): 4820–4. doi:10.1073/pnas.89.11.4820. PMC 49179. PMID 1534408.
  7. ^ "Entrez Gene: ATF4 activating transcription factor 4 (tax-responsive enhancer element B67)".
  8. ^ Franceschi RT, Ge C, Xiao G, Roca H, Jiang D (2009). "Transcriptional regulation of osteoblasts". Cells Tissues Organs. 189 (1–4): 144–52. doi:10.1159/000151747. PMC 3512205. PMID 18728356.
  9. ^ Matsuguchi T, Chiba N, Bandow K, Kakimoto K, Masuda A, Ohnishi T (March 2009). "JNK activity is essential for Atf4 expression and late-stage osteoblast differentiation". Journal of Bone and Mineral Research. 24 (3): 398–410. doi:10.1359/jbmr.081107. PMID 19016586.
  10. ^ Ferraz RC, Camara H, De-Souza EA, Pinto S, Pinca AP, Silva RC, Sato VN, Castilho BA, Mori MA (October 2016). "IMPACT is a GCN2 inhibitor that limits lifespan in Caenorhabditis elegans". BMC Biology. 14 (1): 87. doi:10.1186/s12915-016-0301-2. PMID 27717342.
  11. ^ a b Somers J, Pöyry T, Willis AE (August 2013). "A perspective on mammalian upstream open reading frame function". The International Journal of Biochemistry & Cell Biology. 45 (8): 1690–700. doi:10.1016/j.biocel.2013.04.020. PMID 23624144.

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.