Global InformationTransactivation domain information
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 necessarily mean similar activation pathways, TADs can be grouped by the process they stimulate, either initiation or elongation.[15]
- ^ Wärnmark A, Treuter E, Wright AP, Gustafsson JA (Oct 2003). "Activation functions 1 and 2 of nuclear receptors: molecular strategies for transcriptional activation". Molecular Endocrinology. 17 (10): 1901–9. doi:10.1210/me.2002-0384. PMID 12893880.
- ^ Ma J, Ptashne M (Oct 1987). "A new class of yeast transcriptional activators". Cell. 51 (1): 113–9. doi:10.1016/0092-8674(87)90015-8. PMID 3115591.
- ^ Sadowski I, Ma J, Triezenberg S, Ptashne M (Oct 1988). "GAL4-VP16 is an unusually potent transcriptional activator". Nature. 335 (6190): 563–4. Bibcode:1988Natur.335..563S. doi:10.1038/335563a0. PMID 3047590. S2CID 4276393.
- ^ Sullivan SM, Horn PJ, Olson VA, Koop AH, Niu W, Ebright RH, Triezenberg SJ (Oct 1998). "Mutational analysis of a transcriptional activation region of the VP16 protein of herpes simplex virus". Nucleic Acids Research. 26 (19): 4487–96. doi:10.1093/nar/26.19.4487. PMC 147869. PMID 9742254.
- ^ Gill G, Ptashne M (Oct 1987). "Mutants of GAL4 protein altered in an activation function". Cell. 51 (1): 121–6. doi:10.1016/0092-8674(87)90016-X. PMID 3115592.
- ^ Hope IA, Mahadevan S, Struhl K (Jun 1988). "Structural and functional characterization of the short acidic transcriptional activation region of yeast GCN4 protein". Nature. 333 (6174): 635–40. Bibcode:1988Natur.333..635H. doi:10.1038/333635a0. PMID 3287180. S2CID 2635634.
- ^ Hope IA, Struhl K (Sep 1986). "Functional dissection of a eukaryotic transcriptional activator protein, GCN4 of yeast". Cell. 46 (6): 885–94. doi:10.1016/0092-8674(86)90070-X. PMID 3530496. S2CID 40730692.
- ^ Drysdale CM, Dueñas E, Jackson BM, Reusser U, Braus GH, Hinnebusch AG (Mar 1995). "The transcriptional activator GCN4 contains multiple activation domains that are critically dependent on hydrophobic amino acids". Molecular and Cellular Biology. 15 (3): 1220–33. doi:10.1128/mcb.15.3.1220. PMC 230345. PMID 7862116.
- ^ Regier JL, Shen F, Triezenberg SJ (Feb 1993). "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. Bibcode:1993PNAS...90..883R. doi:10.1073/pnas.90.3.883. PMC 45774. PMID 8381535.
- ^ Mitchell PJ, Tjian R (July 1989). "Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins". Science. 245 (4916): 371–8. Bibcode:1989Sci...245..371M. doi:10.1126/science.2667136. PMID 2667136.
- ^ Sadowski I, Ma J, Triezenberg S, Ptashne M (October 1988). "GAL4-VP16 is an unusually potent transcriptional activator". Nature. 335 (6190): 563–4. Bibcode:1988Natur.335..563S. doi:10.1038/335563a0. PMID 3047590. S2CID 4276393.
- ^ Courey AJ, Holtzman DA, Jackson SP, Tjian R (December 1989). "Synergistic activation by the glutamine-rich domains of human transcription factor Sp1". Cell. 59 (5): 827–36. doi:10.1016/0092-8674(89)90606-5. PMID 2512012. S2CID 2910480.
- ^ Mermod N, O'Neill EA, Kelly TJ, Tjian R (August 1989). "The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain". Cell. 58 (4): 741–53. doi:10.1016/0092-8674(89)90108-6. PMID 2504497. S2CID 22817940.
- ^ Attardi LD, Tjian R (July 1993). "Drosophila tissue-specific transcription factor NTF-1 contains a novel isoleucine-rich activation motif". Genes & Development. 7 (7B): 1341–53. doi:10.1101/gad.7.7b.1341. PMID 8330738.
- ^ Cite error: The named reference
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