ATF4

Activating transcription factor 4 (tax-responsive enhancer element B67)

PDB rendering based on 1ci6.
Identifiers
Symbols ATF4; CREB-2; CREB2; TAXREB67; TXREB
External IDs OMIM: 604064 MGI: 88096 HomoloGene: 1266 GeneCards: ATF4 Gene
Orthologs
Species Human Mouse
Entrez 468 11911
Ensembl ENSG00000128272 ENSMUSG00000042406
UniProt P18848 Q3U2J1
RefSeq (mRNA) NM_001675.2 NM_009716.2
RefSeq (protein) NP_001666.2 NP_033846.2
Location (UCSC) Chr 22:
39.92 – 39.92 Mb		 Chr 15:
80.09 – 80.09 Mb
PubMed search [1] [2]

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.[1][2]

Contents

Function

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.[3]

ATF4 transcription factor is also known to play role in osteoblast differentiation along with RUNX2 and osterix.[4] 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.[5]

Interactions

ATF4 has been shown to interact with POLR2C,[6] TRIB3[7][8] and GABBR1.[9]

See also

References

  1. ^ 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. http://jvi.asm.org/cgi/content/abstract/65/3/1420. 
  2. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=49179. 
  3. ^ "Entrez Gene: ATF4 activating transcription factor 4 (tax-responsive enhancer element B67)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=468. 
  4. ^ 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. PMID 18728356. 
  5. ^ 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 : the Official Journal of the American Society for Bone and Mineral Research 24 (3): 398–410. doi:10.1359/jbmr.081107. PMID 19016586. 
  6. ^ De Angelis, Roberta; Iezzi Simona, Bruno Tiziana, Corbi Nicoletta, Di Padova Monica, Floridi Aristide, Fanciulli Maurizio, Passananti Claudio (Jul. 2003). "Functional interaction of the subunit 3 of RNA polymerase II (RPB3) with transcription factor-4 (ATF4)". FEBS Lett. (Netherlands) 547 (1–3): 15–9. doi:10.1016/S0014-5793(03)00659-8. ISSN 0014-5793. PMID 12860379. 
  7. ^ Bowers, Alex J; Scully Sheila, Boylan John F (May. 2003). "SKIP3, a novel Drosophila tribbles ortholog, is overexpressed in human tumors and is regulated by hypoxia". Oncogene (England) 22 (18): 2823–35. doi:10.1038/sj.onc.1206367. ISSN 0950-9232. PMID 12743605. 
  8. ^ Zhou, Ying; Li Lu, Liu Qiongming, Xing Guichun, Kuai Xuezhang, Sun Jing, Yin Xiushan, Wang Jian, Zhang Lingqiang, He Fuchu (May. 2008). "E3 ubiquitin ligase SIAH1 mediates ubiquitination and degradation of TRB3". Cell. Signal. (England) 20 (5): 942–8. doi:10.1016/j.cellsig.2008.01.010. ISSN 0898-6568. PMID 18276110. 
  9. ^ White, J H; McIllhinney R A, Wise A, Ciruela F, Chan W Y, Emson P C, Billinton A, Marshall F H (Dec. 2000). "The GABAB receptor interacts directly with the related transcription factors CREB2 and ATFx". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (25): 13967–72. doi:10.1073/pnas.240452197. ISSN 0027-8424. PMC 17684. PMID 11087824. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=17684. 

Further reading

External links

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