ATF4
Aktivacijski transkripcijski faktor 4 (taks- pojačivač odgovora B67)', također poznat kao ATF4, je protein koji je kod ljudi kodiran genom ATF4 sa hromosoma 22.[5][6]
Aminokiselinska sekvenca
[uredi | uredi izvor]Dužina polipeptidnojg lanca je 351 aminokiselina, a molekulska težina 38.590 Da.[7]
10 | 20 | 30 | 40 | 50 | ||||
---|---|---|---|---|---|---|---|---|
MTEMSFLSSE | VLVGDLMSPF | DQSGLGAEES | LGLLDDYLEV | AKHFKPHGFS | ||||
SDKAKAGSSE | WLAVDGLVSP | SNNSKEDAFS | GTDWMLEKMD | LKEFDLDALL | ||||
GIDDLETMPD | DLLTTLDDTC | DLFAPLVQET | NKQPPQTVNP | IGHLPESLTK | ||||
PDQVAPFTFL | QPLPLSPGVL | SSTPDHSFSL | ELGSEVDITE | GDRKPDYTAY | ||||
VAMIPQCIKE | EDTPSDNDSG | ICMSPESYLG | SPQHSPSTRG | SPNRSLPSPG | ||||
VLCGSARPKP | YDPPGEKMVA | AKVKGEKLDK | KLKKMEQNKT | AATRYRQKKR | ||||
AEQEALTGEC | KELEKKNEAL | KERADSLAKE | IQYLKDLIEE | VRKARGKKRV | ||||
P |
Funkcija
[uredi | uredi izvor]Ovaj gen kodira transkripcijski faktor, prvobitno identificiran kao široko eksprimirani DNK vezujući protein sisara koji bi mogao vezati pojačivač reakcije na taksov e u LTR HTLV-1. Kodirani protein je takođe izolovan i okarakterisan kao cAMP-odgovorn i element koji vezuje protein 2 (CREB-2). Protein kodiran ovim genom pripada porodici proteina koji se vezuju za DNK koja uključuje porodicu transkripcionih faktora AP-1, cAMP-odgovora elementa vezujućih proteina (CREB) i proteina sličnih CREB-u. Ovi transkripcijski faktori dijele regiju leucinskog zatvarača koja je uključena u interakcije protein-protein, na C-terminalu dijela osnovnih aminokiselina koji funkcionira kao DNK-vezujući domen. Opisana su dva alternativna transkripta koje kodiraju isti protein. Dva pseudogena nalaze se na X hromosomu, regija na q28 koja sadrži veliku obrnutu duplikaciju.[8]
Također je poznato da transkripcijski faktor ATF4 ima ulogu u diferencijaciji osteoblasta, zajedno sa RUNX2 i osteriksom.[9] Terminalna diferencijacija osteoblasta, predstavljena mineralizacijom matriksa, značajno je inhibirana inaktivacijom JNK. Inaktivacija JNK, posljedično smanjuje ekspresiju ATF-4 i mineralizaciju matriksa.[10] Protein IMPACT reguliše ATF4 u C. elegans kako bi produžio životni vijek.[11]
Translacija
[uredi | uredi izvor]Translacija ATF4 ovisi o izvodnom otvorenom okviru čitanje koji se nalazi u 5' UTR-u.[12] Lokacija drugog ORF-a, prikladno nazvanog uORF2, preklapa se sa okvirom otvorenog čitanja ATF4. U normalnim uslovima, uORF1 se prevodi, a zatim se translacija uORF2 dešava tek nakon što se ponovo dobije eIF2-TC. Translacija uORF2 zahtijeva da ribosomi prođu pored "ATF4" ORF, čiji se početni kodon nalazi unutar uORF2. To dovodi do njegove represije. Međutim, tokom stresnih uslova, ribosomski 40S će zaobići uORF2, zbog smanjenja koncentracije eIF2-TC, što znači da nijkedan ribosom ne dobije na vrijeme uputu da prevede uORF2. Umjesto toga, translatira se "ATF4".[12]
Također pogledajte
[uredi | uredi izvor]Reference
[uredi | uredi izvor]- ^ a b c GRCh38: Ensembl release 89: ENSG00000128272 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000042406 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Tsujimoto A, Nyunoya H, Morita T, Sato T, Shimotohno K (mart 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. doi:10.1128/JVI.65.3.1420-1426.1991. PMC 239921. PMID 1847461.
- ^ Karpinski BA, Morle GD, Huggenvik J, Uhler MD, Leiden JM (juni 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. Bibcode:1992PNAS...89.4820K. doi:10.1073/pnas.89.11.4820. PMC 49179. PMID 1534408.
- ^ "UniProt, P18848" (jezik: англ.). Pristupljeno 12-09-2017. Provjerite vrijednost datuma u parametru:
|access-date=
(pomoć)CS1 održavanje: nepoznati jezik (link) - ^ "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. PMC 3512205. PMID 18728356.
- ^ Matsuguchi T, Chiba N, Bandow K, Kakimoto K, Masuda A, Ohnishi T (mart 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. S2CID 13111270.
- ^ Ferraz RC, Camara H, De-Souza EA, Pinto S, Pinca AP, Silva RC, Sato VN, Castilho BA, Mori MA (oktobar 2016). "IMPACT is a GCN2 inhibitor that limits lifespan in Caenorhabditis elegans". BMC Biology. 14 (1): 87. doi:10.1186/s12915-016-0301-2. PMC 5054600. PMID 27717342.
- ^ 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. PMC 7172355. PMID 23624144.
Dopunska literatura
[uredi | uredi izvor]- Rutkowski DT, Kaufman RJ (april 2003). "All roads lead to ATF4". Developmental Cell. 4 (4): 442–4. doi:10.1016/S1534-5807(03)00100-X. PMID 12689582.
- Nishizawa M, Nagata S (mart 1992). "cDNA clones encoding leucine-zipper proteins which interact with G-CSF gene promoter element 1-binding protein". FEBS Letters. 299 (1): 36–8. doi:10.1016/0014-5793(92)80094-W. PMID 1371974. S2CID 34097395.
- Karpinski BA, Morle GD, Huggenvik J, Uhler MD, Leiden JM (juni 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. Bibcode:1992PNAS...89.4820K. doi:10.1073/pnas.89.11.4820. PMC 49179. PMID 1534408.
- Hai T, Curran T (maj 1991). "Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity". Proceedings of the National Academy of Sciences of the United States of America. 88 (9): 3720–4. Bibcode:1991PNAS...88.3720H. doi:10.1073/pnas.88.9.3720. PMC 51524. PMID 1827203.
- Tsujimoto A, Nyunoya H, Morita T, Sato T, Shimotohno K (mart 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. doi:10.1128/JVI.65.3.1420-1426.1991. PMC 239921. PMID 1847461.
- Hai TW, Liu F, Coukos WJ, Green MR (decembar 1989). "Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers". Genes & Development. 3 (12B): 2083–90. doi:10.1101/gad.3.12b.2083. PMID 2516827.
- Kokame K, Kato H, Miyata T (novembar 1996). "Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis. GRP78/BiP and novel genes". The Journal of Biological Chemistry. 271 (47): 29659–65. doi:10.1074/jbc.271.47.29659. PMID 8939898.
- Reddy TR, Tang H, Li X, Wong-Staal F (juni 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 (septembar 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". The Journal of Biological Chemistry. 272 (38): 24088–95. doi:10.1074/jbc.272.38.24088. PMID 9295363.
- Kawai T, Matsumoto M, Takeda K, Sanjo H, Akira S (mart 1998). "ZIP kinase, a novel serine/threonine kinase which mediates apoptosis". Molecular and Cellular Biology. 18 (3): 1642–51. doi:10.1128/mcb.18.3.1642. PMC 108879. PMID 9488481.
- Outinen PA, Sood SK, Pfeifer SI, Pamidi S, Podor TJ, Li J, Weitz JI, Austin RC (august 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. doi:10.1182/blood.V94.3.959.415k20_959_967. PMID 10419887.
- Podust LM, Krezel AM, Kim Y (januar 2001). "Crystal structure of the CCAAT box/enhancer-binding protein beta activating transcription factor-4 basic leucine zipper heterodimer in the absence of DNA". The Journal of Biological Chemistry. 276 (1): 505–13. doi:10.1074/jbc.M005594200. PMID 11018027.
- Murphy P, Kolstø A (oktobar 2000). "Expression of the bZIP transcription factor TCF11 and its potential dimerization partners during development". Mechanisms of Development. 97 (1–2): 141–8. doi:10.1016/S0925-4773(00)00413-5. PMID 11025215. S2CID 17474070.
- White JH, McIllhinney RA, Wise A, Ciruela F, Chan WY, Emson PC, Billinton A, Marshall FH (decembar 2000). "The GABAB receptor interacts directly with the related transcription factors CREB2 and ATFx". Proceedings of the National Academy of Sciences of the United States of America. 97 (25): 13967–72. Bibcode:2000PNAS...9713967W. doi:10.1073/pnas.240452197. PMC 17684. PMID 11087824.
- He CH, Gong P, Hu B, Stewart D, Choi ME, Choi AM, Alam J (juni 2001). "Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation". The Journal of Biological Chemistry. 276 (24): 20858–65. doi:10.1074/jbc.M101198200. PMID 11274184.
- Siu F, Bain PJ, LeBlanc-Chaffin R, Chen H, Kilberg MS (juli 2002). "ATF4 is a mediator of the nutrient-sensing response pathway that activates the human asparagine synthetase gene". The Journal of Biological Chemistry. 277 (27): 24120–7. doi:10.1074/jbc.M201959200. PMID 11960987.
- Bowers AJ, Scully S, Boylan JF (maj 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 (novembar 2009). "Atf4 regulates obesity, glucose homeostasis, and energy expenditure". Diabetes. 58 (11): 2565–73. doi:10.2337/db09-0335. PMC 2768187. PMID 19690063.
- Ebert, S. M., Bullard, S. A., Basisty, N., Marcotte, G. R., Skopec, Z. P., Dierdorff, J. M., ... & Bodine, S. C. (2020). "Activating transcription factor 4 (ATF4) promotes skeletal muscle atrophy by forming a heterodimer with the transcriptional regulator C/EBPβ". Journal of Biological Chemistry, 295(9), 2787–2803. doi:10.1074/jbc.RA119.012095 PMC 7049960 PubMed
Vanjski linkovi
[uredi | uredi izvor]- ATF4 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)
- Lokacija ljudskog genoma ATF4 i stranica sa detaljima o genu ATF4 u UCSC Genome Browseru.
- PDBe-KB provides an overview of all the structure information available in the PDB for Human Cyclic AMP-dependent transcription factor ATF-4
Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.