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- activating transcription factor 4
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出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2014/06/04 14:43:28」(JST)
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Activating transcription factor 4 (tax-responsive enhancer element B67) |
PDB rendering based on 1ci6. |
Available structures |
PDB |
Ortholog search: PDBe, RCSB |
List of PDB id codes |
1CI6
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Identifiers |
Symbols |
ATF4 ; CREB-2; CREB2; TAXREB67; TXREB |
External IDs |
OMIM: 604064 MGI: 88096 HomoloGene: 1266 GeneCards: ATF4 Gene |
Gene ontology |
Molecular function |
• DNA binding
• sequence-specific DNA binding transcription factor activity
• protein binding
• protein C-terminus binding
• sequence-specific DNA binding
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Cellular component |
• nucleus
• nucleoplasm
• transcription factor complex
• cytoplasm
• microtubule organizing center
• dendrite membrane
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Biological process |
• gluconeogenesis
• regulation of transcription, DNA-dependent
• transcription from RNA polymerase II promoter
• cellular amino acid metabolic process
• activation of signaling protein activity involved in unfolded protein response
• gamma-aminobutyric acid signaling pathway
• endoplasmic reticulum unfolded protein response
• response to endoplasmic reticulum stress
• negative regulation of potassium ion transport
• positive regulation of neuron apoptotic process
• cellular protein metabolic process
• positive regulation of transcription, DNA-dependent
• positive regulation of transcription from RNA polymerase II promoter
• intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
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Sources: Amigo / QuickGO |
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Orthologs |
Species |
Human |
Mouse |
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Entrez |
468 |
11911 |
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Ensembl |
ENSG00000128272 |
ENSMUSG00000042406 |
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UniProt |
P18848 |
Q06507 |
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RefSeq (mRNA) |
NM_001675 |
NM_009716 |
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RefSeq (protein) |
NP_001666 |
NP_033846 |
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Location (UCSC) |
Chr 22:
39.92 – 39.92 Mb |
Chr 15:
80.26 – 80.26 Mb |
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PubMed search |
[1] |
[2] |
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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
- 1 Function
- 2 Translation
- 3 Interactions
- 4 See also
- 5 References
- 6 Further reading
- 7 External links
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]
Translation
The translation of ATF4 is dependent on upstream open reading frames located in the 5'UTR.[6] 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.[6]
Interactions
Kir2.1 has been shown to interact with:
- DLG4,[7]
- IL16,[8] and
- TRAK2.[9]
See also
- Activating transcription factor
References
- ^ 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.
- ^ 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.
- ^ "Entrez Gene: ATF4 activating transcription factor 4 (tax-responsive enhancer element B67)".
- ^ 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.
- ^ 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.
- ^ a b Somers J, Pöyry T, Willis AE (August 2013). "A perspective on mammalian upstream open reading frame function". Int. J. Biochem. Cell Biol. 45 (8): 1690–700. doi:10.1016/j.biocel.2013.04.020. PMID 23624144.
- ^ Nehring RB, Wischmeyer E, Döring F, Veh RW, Sheng M, Karschin A (2000). "Neuronal inwardly rectifying K(+) channels differentially couple to PDZ proteins of the PSD-95/SAP90 family". J. Neurosci. 20 (1): 156–62. PMID 10627592.
- ^ Kurschner C, Yuzaki M (1999). "Neuronal interleukin-16 (NIL-16): a dual function PDZ domain protein". J. Neurosci. 19 (18): 7770–80. PMID 10479680.
- ^ Grishin A, Li H, Levitan ES, Zaks-Makhina E (2006). "Identification of gamma-aminobutyric acid receptor-interacting factor 1 (TRAK2) as a trafficking factor for the K+ channel Kir2.1". J. Biol. Chem. 281 (40): 30104–11. doi:10.1074/jbc.M602439200. PMID 16895905.
Further reading
- Rutkowski DT, Kaufman RJ (2003). "All roads lead to ATF4". Dev. Cell 4 (4): 442–4. doi:10.1016/S1534-5807(03)00100-X. PMID 12689582.
- Nishizawa M, Nagata S (1992). "cDNA clones encoding leucine-zipper proteins which interact with G-CSF gene promoter element 1-binding protein". FEBS Lett. 299 (1): 36–8. doi:10.1016/0014-5793(92)80094-W. PMID 1371974.
- Karpinski BA, Morle GD, Huggenvik J et al. (1992). "Molecular cloning of human CREB-2: an ATF/CREB transcription factor that can negatively regulate transcription from the cAMP response element". Proc. Natl. Acad. Sci. U.S.A. 89 (11): 4820–4. doi:10.1073/pnas.89.11.4820. PMC 49179. PMID 1534408.
- Hai T, Curran T (1991). "Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity". Proc. Natl. Acad. Sci. U.S.A. 88 (9): 3720–4. doi:10.1073/pnas.88.9.3720. PMC 51524. PMID 1827203.
- Tsujimoto A, Nyunoya H, Morita T et al. (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". J. Virol. 65 (3): 1420–6. PMC 239921. PMID 1847461.
- Hai TW, Liu F, Coukos WJ, Green MR (1990). "Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers". Genes Dev. 3 (12B): 2083–90. doi:10.1101/gad.3.12b.2083. PMID 2516827.
- Kokame K, Kato H, Miyata T (1997). "Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis. GRP78/BiP and novel genes". J. Biol. Chem. 271 (47): 29659–65. doi:10.1074/jbc.271.47.29659. PMID 8939898.
- Reddy TR, Tang H, Li X, Wong-Staal F (1997). "Functional interaction of the HTLV-1 transactivator Tax with activating transcription factor-4 (ATF4)". Oncogene 14 (23): 2785–92. doi:10.1038/sj.onc.1201119. PMID 9190894.
- Liang G, Hai T (1997). "Characterization of human activating transcription factor 4, a transcriptional activator that interacts with multiple domains of cAMP-responsive element-binding protein (CREB)-binding protein". J. Biol. Chem. 272 (38): 24088–95. doi:10.1074/jbc.272.38.24088. PMID 9295363.
- Kawai T, Matsumoto M, Takeda K et al. (1998). "ZIP Kinase, a Novel Serine/Threonine Kinase Which Mediates Apoptosis". Mol. Cell. Biol. 18 (3): 1642–51. PMC 108879. PMID 9488481.
- Outinen PA, Sood SK, Pfeifer SI et al. (1999). "Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells". Blood 94 (3): 959–67. PMID 10419887.
- Dunham I, Shimizu N, Roe BA et al. (1999). "The DNA sequence of human chromosome 22". Nature 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208.
- Podust LM, Krezel AM, Kim Y (2001). "Crystal structure of the CCAAT box/enhancer-binding protein beta activating transcription factor-4 basic leucine zipper heterodimer in the absence of DNA". J. Biol. Chem. 276 (1): 505–13. doi:10.1074/jbc.M005594200. PMID 11018027.
- Murphy P, Kolstø A (2001). "Expression of the bZIP transcription factor TCF11 and its potential dimerization partners during development". Mech. Dev. 97 (1–2): 141–8. doi:10.1016/S0925-4773(00)00413-5. PMID 11025215.
- White JH, McIllhinney RA, Wise A et al. (2001). "The GABAB receptor interacts directly with the related transcription factors CREB2 and ATFx". Proc. Natl. Acad. Sci. U.S.A. 97 (25): 13967–72. doi:10.1073/pnas.240452197. PMC 17684. PMID 11087824.
- He CH, Gong P, Hu B et al. (2001). "Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation". J. Biol. Chem. 276 (24): 20858–65. doi:10.1074/jbc.M101198200. PMID 11274184.
- Siu F, Bain PJ, LeBlanc-Chaffin R et al. (2002). "ATF4 is a mediator of the nutrient-sensing response pathway that activates the human asparagine synthetase gene". J. Biol. Chem. 277 (27): 24120–7. doi:10.1074/jbc.M201959200. PMID 11960987.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Bowers AJ, Scully S, Boylan JF (2003). "SKIP3, a novel Drosophila tribbles ortholog, is overexpressed in human tumors and is regulated by hypoxia". Oncogene 22 (18): 2823–35. doi:10.1038/sj.onc.1206367. PMID 12743605.
- Seo J, Fortuno ES, Suh JM, Stenesen D, Tang W, Parks EJ, Adams CM, Townes T, Graff JM (2009). "Atf4 Regulates Obesity, Glucose Homeostasis, and Energy Expenditure". Diabetes 58 (11): 2565–2573. doi:10.2337/db09-0335. PMC 2768187. PMID 19690063.
External links
- ATF4 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
PDB gallery
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1ci6: TRANSCRIPTION FACTOR ATF4-C/EBP BETA BZIP HETERODIMER
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Transcription factors and intracellular receptors
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(1) Basic domains
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(1.1) Basic leucine zipper (bZIP) |
- Activating transcription factor
- AP-1
- c-Fos
- FOSB
- FOSL1
- FOSL2
- JDP2
- c-Jun
- JUNB
- JunD
- BACH
- BATF
- BLZF1
- C/EBP
- CREB
- CREM
- DBP
- DDIT3
- GABPA
- HLF
- MAF
- NFE
- NFIL3
- NRL
- NRF
- XBP1
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(1.2) Basic helix-loop-helix (bHLH) |
- ATOH1
- AhR
- AHRR
- ARNT
- ASCL1
- BHLH
- ARNTL
- CLOCK
- EPAS1
- FIGLA
- HAND
- HES
- HEY
- HES1
- HIF
- ID
- LYL1
- MESP2
- MXD4
- MYCL1
- MYCN
- Myogenic regulatory factors
- Neurogenins
- NeuroD
- NPAS
- OLIG
- Pho4
- Scleraxis
- SIM
- TAL
- Twist
- USF1
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(1.3) bHLH-ZIP |
- AP-4
- MAX
- MITF
- MNT
- MLX
- MXI1
- Myc
- SREBP
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(1.4) NF-1 |
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(1.5) RF-X |
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(1.6) Basic helix-span-helix (bHSH) |
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(2) Zinc finger DNA-binding domains
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(2.1) Nuclear receptor (Cys4) |
subfamily 1 |
- Thyroid hormone
- CAR
- FXR
- LXR
- PPAR
- PXR
- RAR
- ROR
- Rev-ErbA
- VDR
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subfamily 2 |
- COUP-TF
- Ear-2
- HNF4
- PNR
- RXR
- Testicular receptor
- TLX
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subfamily 3 |
- Steroid hormone
- Androgen
- Estrogen
- Glucocorticoid
- Mineralocorticoid
- Progesterone
- Estrogen related
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subfamily 4 |
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subfamily 5 |
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subfamily 6 |
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subfamily 0 |
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(2.2) Other Cys4 |
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(2.3) Cys2His2 |
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(2.4) Cys6 |
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(2.5) Alternating composition |
- AIRE
- DIDO1
- GRLF1
- ING
- JARID
- JMJD1B
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(2.6) WRKY |
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(3) Helix-turn-helix domains
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(4) β-Scaffold factors with minor groove contacts
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(4.1) Rel homology region |
- NF-κB
- NFKB1
- NFKB2
- REL
- RELA
- RELB
- NFAT
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(4.2) STAT |
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(4.3) p53 |
- p53
- TBX
- 1
- 2
- 3
- 5
- 19
- 21
- 22
- TBR1
- TBR2
- TFT
- MYRF
- TP63
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(4.4) MADS box |
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(4.6) TATA-binding proteins |
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(4.7) High-mobility group |
- BBX
- HMGB
- HMGN
- HNF
- LEF1
- SOX
- 1
- 2
- 3
- 4
- 5
- 6
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 18
- 21
- SRY
- SSRP1
- TCF
- TOX
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(4.9) Grainyhead |
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(4.10) Cold-shock domain |
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(4.11) Runt |
- CBF
- CBFA2T2
- CBFA2T3
- RUNX1
- RUNX2
- RUNX3
- RUNX1T1
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(0) Other transcription factors
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(0.2) HMGI(Y) |
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(0.3) Pocket domain |
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(0.5) AP-2/EREBP-related factors |
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(0.6) Miscellaneous |
- ARID
- CAP
- IFI
- MLL
- MNDA
- NFY
- Rho/Sigma
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see also transcription factor/coregulator deficiencies
B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)
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Regulome
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Activates |
Runx2, nrf1,Bip
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Inhibits |
ATF4, CHOP
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Is activated by |
not, PERK
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UpToDate Contents
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English Journal
- Endoplasmic reticulum stress does not contribute to steatohepatitis in obese and insulin-resistant high-fat-diet-fed foz/foz mice.
- Legry V1, Van Rooyen DM2, Lambert B1, Sempoux C3, Poekes L1, Español-Suñer R1, Molendi-Coste O1, Horsmans Y1, Farrell GC2, Leclercq IA1.
- Clinical science (London, England : 1979).Clin Sci (Lond).2014 Oct;127(7):507-18. doi: 10.1042/CS20140026.
- Non-alcoholic fatty liver (steatosis) and steatohepatitis [non-alcoholic steatohepatitis (NASH)] are hepatic complications of the metabolic syndrome. Endoplasmic reticulum (ER) stress is proposed as a crucial disease mechanism in obese and insulin-resistant animals (such as ob/ob mice) with simple s
- PMID 24766485
- PERK mediates eIF2α phosphorylation responsible for BACE1 elevation, CREB dysfunction and neurodegeneration in a mouse model of Alzheimer's disease.
- Devi L1, Ohno M2.
- Neurobiology of aging.Neurobiol Aging.2014 Oct;35(10):2272-81. doi: 10.1016/j.neurobiolaging.2014.04.031. Epub 2014 May 2.
- Emerging evidence suggests that aberrant phosphorylation of eukaryotic initiation factor-2α (eIF2α) may induce synaptic failure and neurodegeneration through persistent translational inhibition of global protein synthesis. However, elevated phospho-eIF2α also paradoxically causes translational ac
- PMID 24889041
- Nrf2- and ATF4-Dependent Upregulation of xCT Modulates the Sensitivity of T24 Bladder Carcinoma Cells to Proteasome Inhibition.
- Ye P1, Mimura J2, Okada T3, Sato H3, Liu T1, Maruyama A1, Ohyama C4, Itoh K1.
- Molecular and cellular biology.Mol Cell Biol.2014 Sep 15;34(18):3421-34. doi: 10.1128/MCB.00221-14. Epub 2014 Jul 7.
- The ubiquitin-proteasome pathway degrades ubiquitinated proteins to remove damaged or misfolded protein and thus plays an important role in the maintenance of many important cellular processes. Because the pathway is also crucial for tumor cell growth and survival, proteasome inhibition by specific
- PMID 25002527
Japanese Journal
- Selective Regulation of FGF19 and FGF21 Expression by Cellular and Nutritional Stress
- SHIMIZU Makoto,MORIMOTO Hitomi,MARUYAMA Ryuto [他]
- Journal of nutritional science and vitaminology 61(2), 154-160, 2015-04
- NAID 40020457897
- Selective Regulation of FGF19 and FGF21 Expression by Cellular and Nutritional Stress
- , , , ,
- Journal of Nutritional Science and Vitaminology 61(2), 154-160, 2015
- … FGF19 and FGF21 were recently identified as targets of activating transcription factor 4 (ATF4), which is activated in response to endoplasmic reticulum (ER) stress. … ATF4 is also activated by oxidative stress and amino acid deprivation. … These results indicate distinctive patterns of regulation of FGF19 expression by ER stress, and FGF21 expression by ER stress, oxidative stress, and amino acid deprivation through ATF4 activation. …
- NAID 130005074124
- Tauroursodeoxycholic acid attenuates inorganic phosphate-induced osteoblastic differentiation and mineralization in NIH3T3 fibroblasts by inhibiting the ER stress response PERK-eIF2α-ATF4 pathway
- , , , , ,
- Drug Discoveries & Therapeutics 9(1), 38-44, 2015
- … Mechanistically, TUDCA inhibited the ER stress response PERK-eIF2α-ATF4 pathway during osteogenesis. … In conclusion, TUDCA could inhibit fibroblasts mineralization via supressing the ER stress response PERK-eIF2α-ATF4 pathway, and has potential pharmacologic and therapeutic applications for treating ectopic ossification associated diseases. …
- NAID 130005054803
Related Links
- ATF4 transcription factor is also known to play role in osteoblast differentiation along with RUNX2 and osterix. Terminal osteoblast differentiation, represented by matrix mineralization, is significantly inhibited by the inactivation of JNK.
- Complete information for ATF4 gene (protein-coding), activating transcription factor 4 (tax-responsive enhancer element B67)
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★リンクテーブル★
[★]
活性化転写因子4、転写因子ATF4
- 関
- ATF4
[★]
- 英
- activating transcription factor 4、ATF4
- 関
- 活性化転写因子4
[★]
[★]
- 関
- activating transcription factor