| Structural highlights
Function
[ATF4_HUMAN] Transcriptional activator. Binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production (By similarity). It binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I. Regulates the induction of DDIT3/CHOP and asparagine synthetase (ASNS) in response to ER stress. In concert with DDIT3/CHOP, activates the transcription of TRIB3 and promotes ER stress-induced neuronal apoptosis by regulating the transcriptional induction of BBC3/PUMA.[1] [2] [3] [CEBPB_MOUSE] Involved in interleukin-6 signal transduction, including the transcriptional activation of acute-phase genes. Functions in brown adipose tissue (BAT) differentiation. Regulates the transcriptional induction of peroxisome proliferator-activated receptor gamma (PPARG).[4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The crystal structure of the heterodimer formed by the basic leucine zipper (bZIP) domains of activating transcription factor-4 (ATF4) and CCAAT box/enhancer-binding protein beta (C/EBP beta), from two different bZIP transcription factor families, has been determined and refined to 2.6 A. The structure shows that the heterodimer forms an asymmetric coiled-coil. Even in the absence of DNA, the basic region of ATF4 forms a continuous alpha-helix, but the basic region of C/EBP beta is disordered. Proteolysis, electrophoretic mobility shift assay, circular dichroism, and NMR analyses indicated that (i) the bZIP domain of ATF4 is a disordered monomer and forms a homodimer upon binding to the DNA target; (ii) the bZIP domain of ATF4 forms a heterodimer with the bZIP domain of C/EBP beta that binds the cAMP response element, but not CCAAT box DNA, with high affinity; and (iii) the basic region of ATF4 has a higher alpha-helical propensity than that of C/EBP beta. These results suggest that the degree of ordering of the basic region and the fork and the dimerization properties of the leucine zipper combine to distinguish the structurally similar bZIP domains of ATF4 and C/EBP beta with respect to DNA target sequence. This study provides insight into the mechanism by which dimeric bZIP transcription factors discriminate between closely related but distinct DNA targets.
Crystal structure of the CCAAT box/enhancer-binding protein beta activating transcription factor-4 basic leucine zipper heterodimer in the absence of DNA.,Podust LM, Krezel AM, Kim Y J Biol Chem. 2001 Jan 5;276(1):505-13. PMID:11018027[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ohoka N, Yoshii S, Hattori T, Onozaki K, Hayashi H. TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. EMBO J. 2005 Mar 23;24(6):1243-55. Epub 2005 Mar 10. PMID:15775988 doi:http://dx.doi.org/10.1038/sj.emboj.7600596
- ↑ Sayer JA, Otto EA, O'Toole JF, Nurnberg G, Kennedy MA, Becker C, Hennies HC, Helou J, Attanasio M, Fausett BV, Utsch B, Khanna H, Liu Y, Drummond I, Kawakami I, Kusakabe T, Tsuda M, Ma L, Lee H, Larson RG, Allen SJ, Wilkinson CJ, Nigg EA, Shou C, Lillo C, Williams DS, Hoppe B, Kemper MJ, Neuhaus T, Parisi MA, Glass IA, Petry M, Kispert A, Gloy J, Ganner A, Walz G, Zhu X, Goldman D, Nurnberg P, Swaroop A, Leroux MR, Hildebrandt F. The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4. Nat Genet. 2006 Jun;38(6):674-81. Epub 2006 May 7. PMID:16682973 doi:http://dx.doi.org/10.1038/ng1786
- ↑ Su N, Kilberg MS. C/EBP homology protein (CHOP) interacts with activating transcription factor 4 (ATF4) and negatively regulates the stress-dependent induction of the asparagine synthetase gene. J Biol Chem. 2008 Dec 12;283(50):35106-17. doi: 10.1074/jbc.M806874200. Epub 2008, Oct 21. PMID:18940792 doi:http://dx.doi.org/10.1074/jbc.M806874200
- ↑ Kajimura S, Seale P, Kubota K, Lunsford E, Frangioni JV, Gygi SP, Spiegelman BM. Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature. 2009 Aug 27;460(7259):1154-8. Epub 2009 Jul 29. PMID:19641492 doi:http://dx.doi.org/nature08262
- ↑ Podust LM, Krezel AM, Kim Y. 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. 2001 Jan 5;276(1):505-13. PMID:11018027 doi:http://dx.doi.org/10.1074/jbc.M005594200
|
