Biology:Transactivation domain

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Short description: Transcription factor scaffold domain

The transactivation domain or trans-activating domain (TAD) is a transcription factor scaffold domain which contains binding sites for other proteins such as transcription coregulators. These binding sites are frequently referred to as activation functions (AFs).[1] TADs are named after their amino acid composition. These amino acids are either essential for the activity or simply the most abundant in the TAD. Transactivation by the Gal4 transcription factor is mediated by acidic amino acids, whereas hydrophobic residues in Gcn4 play a similar role. Hence, the TADs in Gal4 and Gcn4 are referred to as acidic or hydrophobic, respectively.[2][3][4][5][6][7][8][9]

In general we can distinguish four classes of TADs:[10]

  • acidic domains (called also “acid blobs” or “negative noodles", rich in D and E amino acids, present in Gal4, Gcn4 and VP16).[11]
  • glutamine-rich domains (contains multiple repetitions like "QQQXXXQQQ", present in SP1)[12]
  • proline-rich domains (contains repetitions like "PPPXXXPPP" present in c-jun, AP2 and Oct-2)[13]
  • isoleucine-rich domains (repetitions "IIXXII", present in NTF-1)[14]

Alternatively, since similar amino acid compositions does not necessary mean similar activation pathways, TADs can be grouped by the process they stimulate, either initiation or elongation.[15]

Acidic/9aaTAD

9aaTAD-KIX domain complexes

Nine-amino-acid transactivation domain (9aaTAD) defines a domain common to a large superfamily of eukaryotic transcription factors represented by Gal4, Oaf1, Leu3, Rtg3, Pho4, Gln3, Gcn4 in yeast, and by p53, NFAT, NF-κB and VP16 in mammals. The definition largely overlaps with an "acidic" family definition. A 9aaTAD prediction tool is available.[16] 9aaTADs tend to have an associated 3-aa hydrophobic (usually Leu-rich) region immediately to its N-terminal.[17]

9aaTAD transcription factors p53, VP16, MLL, E2A, HSF1, NF-IL6, NFAT1 and NF-κB interact directly with the general coactivators TAF9 and CBP/p300.[16][18][19][20][21][22][23][24][25][26][27][28][29] p53 9aaTADs interact with TAF9, GCN5 and with multiple domains of CBP/p300 (KIX, TAZ1,TAZ2 and IBiD).[30][31][32][33][34]

The KIX domain of general coactivators Med15(Gal11) interacts with 9aaTAD transcription factors Gal4, Pdr1, Oaf1, Gcn4, VP16, Pho4, Msn2, Ino2 and P201. Positions 1, 3-4, and 7 of the 9aaTAD are the main residues that interact with KIX.[35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] Interactions of Gal4, Pdr1 and Gcn4 with Taf9 have been observed.[8][51][52] 9aaTAD is a common transactivation domain which recruits multiple general coactivators TAF9, MED15, CBP/p300 and GCN5.[16]

Example 9aaTADs and KIX interactions[17]
Source 9aaTAD Peptide-KIX interaction (NMR)
p53 TAD1 E TFSD LWKL LSPEETFSDLWKLPE
p53 TAD2 D DIEQ WFTE QAMDDLMLSPDDIEQWFTEDPGPD
MLL S DIMD FVLK DCGNILPSDIMDFVLKNTP
E2A D LLDF SMMF PVGTDKELSDLLDFSMMFPLPVT
Rtg3 E TLDF SLVT E2A homolog
CREB R KILN DLSS RREILSRRPSYRKILNDLSSDAP
CREBaB6 E AILA ELKK CREB-mutant binding to KIX
Gli3 D DVVQ YLNS TAD homology to CREB/KIX
Gal4 D DVYN YLFD Pdr1 and Oaf1 homolog
Oaf1 D LFDY DFLV DLFDYDFLV
Pip2 D FFDY DLLF Oafl homolog
Pdr1 E DLYS ILWS EDLYSILWSDWY
Pdr3 T DLYH TLWN Pdr1 homolog

Glutamine-rich

Glutamine (Q)-rich TADs are found in POU2F1 (Oct1), POU2F2 (Oct2), and Sp1 (see also Sp/KLF family).[12] Although such is not the case for every Q-rich TAD, Sp1 is shown to interact with TAF4 (TAFII 130), a part of the TFIID assembly.[15][53]

See also

References

  1. ↑ "Activation functions 1 and 2 of nuclear receptors: molecular strategies for transcriptional activation". Molecular Endocrinology 17 (10): 1901–9. Oct 2003. doi:10.1210/me.2002-0384. PMID 12893880. 
  2. ↑ "A new class of yeast transcriptional activators". Cell 51 (1): 113–9. Oct 1987. doi:10.1016/0092-8674(87)90015-8. PMID 3115591. 
  3. ↑ "GAL4-VP16 is an unusually potent transcriptional activator". Nature 335 (6190): 563–4. Oct 1988. doi:10.1038/335563a0. PMID 3047590. Bibcode: 1988Natur.335..563S. 
  4. ↑ "Mutational analysis of a transcriptional activation region of the VP16 protein of herpes simplex virus". Nucleic Acids Research 26 (19): 4487–96. Oct 1998. doi:10.1093/nar/26.19.4487. PMID 9742254. 
  5. ↑ "Mutants of GAL4 protein altered in an activation function". Cell 51 (1): 121–6. Oct 1987. doi:10.1016/0092-8674(87)90016-X. PMID 3115592. 
  6. ↑ "Structural and functional characterization of the short acidic transcriptional activation region of yeast GCN4 protein". Nature 333 (6174): 635–40. Jun 1988. doi:10.1038/333635a0. PMID 3287180. Bibcode: 1988Natur.333..635H. 
  7. ↑ "Functional dissection of a eukaryotic transcriptional activator protein, GCN4 of yeast". Cell 46 (6): 885–94. Sep 1986. doi:10.1016/0092-8674(86)90070-X. PMID 3530496. 
  8. ↑ 8.0 8.1 "The transcriptional activator GCN4 contains multiple activation domains that are critically dependent on hydrophobic amino acids". Molecular and Cellular Biology 15 (3): 1220–33. Mar 1995. doi:10.1128/mcb.15.3.1220. PMID 7862116. 
  9. ↑ "Pattern of aromatic and hydrophobic amino acids critical for one of two subdomains of the VP16 transcriptional activator". Proceedings of the National Academy of Sciences of the United States of America 90 (3): 883–7. Feb 1993. doi:10.1073/pnas.90.3.883. PMID 8381535. Bibcode: 1993PNAS...90..883R. 
  10. ↑ "Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins". Science 245 (4916): 371–8. July 1989. doi:10.1126/science.2667136. PMID 2667136. Bibcode: 1989Sci...245..371M. 
  11. ↑ "GAL4-VP16 is an unusually potent transcriptional activator". Nature 335 (6190): 563–4. October 1988. doi:10.1038/335563a0. PMID 3047590. Bibcode: 1988Natur.335..563S. 
  12. ↑ 12.0 12.1 "Synergistic activation by the glutamine-rich domains of human transcription factor Sp1". Cell 59 (5): 827–36. December 1989. doi:10.1016/0092-8674(89)90606-5. PMID 2512012. 
  13. ↑ "The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain". Cell 58 (4): 741–53. August 1989. doi:10.1016/0092-8674(89)90108-6. PMID 2504497. 
  14. ↑ "Drosophila tissue-specific transcription factor NTF-1 contains a novel isoleucine-rich activation motif". Genes & Development 7 (7B): 1341–53. July 1993. doi:10.1101/gad.7.7b.1341. PMID 8330738. 
  15. ↑ 15.0 15.1 Frietze, Seth; Farnham, Peggy J. (14 April 2011). "Transcription Factor Effector Domains". A Handbook of Transcription Factors. Subcellular Biochemistry. 52. pp. 261–277. doi:10.1007/978-90-481-9069-0_12. ISBN 978-90-481-9068-3. 
  16. ↑ 16.0 16.1 16.2 "Nine-amino-acid transactivation domain: establishment and prediction utilities". Genomics 89 (6): 756–68. Jun 2007. doi:10.1016/j.ygeno.2007.02.003. PMID 17467953. 
  17. ↑ 17.0 17.1 "The 9aaTAD Transactivation Domains: From Gal4 to p53". PLOS ONE 11 (9): e0162842. 12 September 2016. doi:10.1371/journal.pone.0162842. PMID 27618436. Bibcode: 2016PLoSO..1162842P. 
  18. ↑ "The alpha-helical FXXPhiPhi motif in p53: TAF interaction and discrimination by MDM2". Proceedings of the National Academy of Sciences of the United States of America 96 (26): 14801–6. Dec 1999. doi:10.1073/pnas.96.26.14801. PMID 10611293. Bibcode: 1999PNAS...9614801U. 
  19. ↑ "Induced alpha helix in the VP16 activation domain upon binding to a human TAF". Science 277 (5330): 1310–3. Aug 1997. doi:10.1126/science.277.5330.1310. PMID 9271577. 
  20. ↑ "Divergent hTAFII31-binding motifs hidden in activation domains". The Journal of Biological Chemistry 275 (21): 15912–6. May 2000. doi:10.1074/jbc.275.21.15912. PMID 10821850. 
  21. ↑ "Mapping the interactions of the p53 transactivation domain with the KIX domain of CBP". Biochemistry 48 (10): 2115–24. Mar 2009. doi:10.1021/bi802055v. PMID 19220000. 
  22. ↑ "Cooperativity in transcription factor binding to the coactivator CREB-binding protein (CBP). The mixed lineage leukemia protein (MLL) activation domain binds to an allosteric site on the KIX domain". The Journal of Biological Chemistry 277 (45): 43168–74. Nov 2002. doi:10.1074/jbc.M207660200. PMID 12205094. 
  23. ↑ "Solution structure of the KIX domain of CBP bound to the transactivation domain of CREB: a model for activator:coactivator interactions". Cell 91 (6): 741–52. Dec 1997. doi:10.1016/S0092-8674(00)80463-8. PMID 9413984. 
  24. ↑ "Roles of phosphorylation and helix propensity in the binding of the KIX domain of CREB-binding protein by constitutive (c-Myb) and inducible (CREB) activators". The Journal of Biological Chemistry 277 (44): 42241–8. Nov 2002. doi:10.1074/jbc.M207361200. PMID 12196545. 
  25. ↑ "Direct observation of the dynamic process underlying allosteric signal transmission". Journal of the American Chemical Society 131 (8): 3063–8. Mar 2009. doi:10.1021/ja809947w. PMID 19203263. 
  26. ↑ "NF-kappaB/p65 antagonizes Nrf2-ARE pathway by depriving CBP from Nrf2 and facilitating recruitment of HDAC3 to MafK". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1783 (5): 713–27. May 2008. doi:10.1016/j.bbamcr.2008.01.002. PMID 18241676. 
  27. ↑ "Critical role for a single leucine residue in leukemia induction by E2A-PBX1". Molecular and Cellular Biology 26 (17): 6442–52. Sep 2006. doi:10.1128/MCB.02025-05. PMID 16914730. 
  28. ↑ "Nuclear factor of activated T cells (NFAT)-dependent transactivation regulated by the coactivators p300/CREB-binding protein (CBP)". The Journal of Experimental Medicine 187 (12): 2031–6. Jun 1998. doi:10.1084/jem.187.12.2031. PMID 9625762. 
  29. ↑ "Interaction and functional collaboration of p300 and C/EBPbeta". Molecular and Cellular Biology 17 (11): 6609–17. Nov 1997. doi:10.1128/mcb.17.11.6609. PMID 9343424. 
  30. ↑ "Four domains of p300 each bind tightly to a sequence spanning both transactivation subdomains of p53". Proceedings of the National Academy of Sciences of the United States of America 104 (17): 7009–14. Apr 2007. doi:10.1073/pnas.0702010104. PMID 17438265. Bibcode: 2007PNAS..104.7009T. 
  31. ↑ "Regulation by phosphorylation of the relative affinities of the N-terminal transactivation domains of p53 for p300 domains and Mdm2". Oncogene 28 (20): 2112–8. May 2009. doi:10.1038/onc.2009.71. PMID 19363523. 
  32. ↑ "Structural basis for p300 Taz2-p53 TAD1 binding and modulation by phosphorylation". Structure 17 (2): 202–10. Feb 2009. doi:10.1016/j.str.2008.12.009. PMID 19217391. 
  33. ↑ "Cooperative regulation of p53 by modulation of ternary complex formation with CBP/p300 and HDM2". Proceedings of the National Academy of Sciences of the United States of America 106 (16): 6591–6. Apr 2009. doi:10.1073/pnas.0811023106. PMID 19357310. Bibcode: 2009PNAS..106.6591F. 
  34. ↑ "Multivalent binding of p53 to the STAGA complex mediates coactivator recruitment after UV damage". Molecular and Cellular Biology 28 (8): 2517–27. Apr 2008. doi:10.1128/MCB.01461-07. PMID 18250150. 
  35. ↑ "A genome-wide analysis of transcriptional effect of Gal11 in Saccharomyces cerevisiae: an application of "mini-array hybridization technique"". DNA Research 8 (1): 23–31. Feb 2001. doi:10.1093/dnares/8.1.23. PMID 11258797. 
  36. ↑ "Proteins that genetically interact with the Saccharomyces cerevisiae transcription factor Gal11p emphasize its role in the initiation-elongation transition". Molecular Genetics and Genomics 265 (6): 1076–86. Aug 2001. doi:10.1007/s004380100505. PMID 11523780. 
  37. ↑ "A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II". Cell 77 (4): 599–608. May 1994. doi:10.1016/0092-8674(94)90221-6. PMID 8187178. 
  38. ↑ "GAL11 protein, an auxiliary transcription activator for genes encoding galactose-metabolizing enzymes in Saccharomyces cerevisiae". Molecular and Cellular Biology 8 (11): 4991–9. Nov 1988. doi:10.1128/mcb.8.11.4991. PMID 3062377. 
  39. ↑ "The Saccharomyces cerevisiae SPT13/GAL11 gene has both positive and negative regulatory roles in transcription". Molecular and Cellular Biology 9 (12): 5602–9. Dec 1989. doi:10.1128/mcb.9.12.5602. PMID 2685570. 
  40. ↑ "In vivo requirement of activator-specific binding targets of mediator". Molecular and Cellular Biology 20 (23): 8709–19. Dec 2000. doi:10.1128/mcb.20.23.8709-8719.2000. PMID 11073972. 
  41. ↑ "A target essential for the activity of a nonacidic yeast transcriptional activator". Proceedings of the National Academy of Sciences of the United States of America 99 (13): 8591–6. Jun 2002. doi:10.1073/pnas.092263499. PMID 12084920. Bibcode: 2002PNAS...99.8591L. 
  42. ↑ "A multiplicity of coactivators is required by Gcn4p at individual promoters in vivo". Molecular and Cellular Biology 23 (8): 2800–20. Apr 2003. doi:10.1128/MCB.23.8.2800-2820.2003. PMID 12665580. 
  43. ↑ "Independent recruitment in vivo by Gal4 of two complexes required for transcription". Molecular Cell 11 (5): 1301–9. May 2003. doi:10.1016/S1097-2765(03)00144-8. PMID 12769853. 
  44. ↑ "Function of a eukaryotic transcription activator during the transcription cycle". Molecular Cell 18 (3): 369–78. Apr 2005. doi:10.1016/j.molcel.2005.03.029. PMID 15866178. 
  45. ↑ "Gal11p dosage-compensates transcriptional activator deletions via Taf14p". Journal of Molecular Biology 374 (1): 9–23. Nov 2007. doi:10.1016/j.jmb.2007.09.013. PMID 17919657. 
  46. ↑ "Role of Gal11, a component of the RNA polymerase II mediator in stress-induced hyperphosphorylation of Msn2 in Saccharomyces cerevisiae". Molecular Microbiology 62 (2): 438–52. Oct 2006. doi:10.1111/j.1365-2958.2006.05363.x. PMID 17020582. 
  47. ↑ "TFIIB and subunits of the SAGA complex are involved in transcriptional activation of phospholipid biosynthetic genes by the regulatory protein Ino2 in the yeast Saccharomyces cerevisiae". Molecular Microbiology 48 (4): 1119–30. May 2003. doi:10.1046/j.1365-2958.2003.03501.x. PMID 12753200. 
  48. ↑ "Gal11 is a general activator of basal transcription, whose activity is regulated by the general repressor Sin4 in yeast". Molecular Genetics and Genomics 269 (1): 68–77. Apr 2003. doi:10.1007/s00438-003-0810-x. PMID 12715155. 
  49. ↑ "A nuclear receptor-like pathway regulating multidrug resistance in fungi". Nature 452 (7187): 604–9. Apr 2008. doi:10.1038/nature06836. PMID 18385733. Bibcode: 2008Natur.452..604T. 
  50. ↑ "Mediator subunit Gal11p/MED15 is required for fatty acid-dependent gene activation by yeast transcription factor Oaf1p". The Journal of Biological Chemistry 284 (7): 4422–8. Feb 2009. doi:10.1074/jbc.M808263200. PMID 19056732. 
  51. ↑ "Use of a genetically introduced cross-linker to identify interaction sites of acidic activators within native transcription factor IID and SAGA". The Journal of Biological Chemistry 278 (9): 6779–86. Feb 2003. doi:10.1074/jbc.M212514200. PMID 12501245. 
  52. ↑ "TFIID and Spt-Ada-Gcn5-acetyltransferase functions probed by genome-wide synthetic genetic array analysis using a Saccharomyces cerevisiae taf9-ts allele". Genetics 171 (3): 959–73. Nov 2005. doi:10.1534/genetics.105.046557. PMID 16118188. 
  53. ↑ "Interaction between intrinsically disordered regions in transcription factors Sp1 and TAF4". Protein Science 25 (11): 2006–2017. November 2016. doi:10.1002/pro.3013. PMID 27515574. 

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