| Structural highlights
Function
RUVB1_HUMAN Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (3' to 5') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity.[1] [2] [3] [4] [5] Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage.[6] [7] [8] [9] [10] Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.[11] [12] [13] [14] [15] Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex. Essential for cell proliferation.[16] [17] [18] [19] [20] May be able to bind plasminogen at cell surface and enhance plasminogen activation.[21] [22] [23] [24] [25]
Publication Abstract from PubMed
The human NuA4/TIP60 co-activator complex, a fusion of the yeast SWR1 and NuA4 complexes, both incorporates the histone variant H2A.Z into nucleosomes and acetylates histones H4/H2A/H2A.Z to regulate gene expression and maintain genome stability. Our cryo-electron microscopy studies show that, within the NuA4/TIP60 complex, the EP400 subunit serves as a scaffold holding the different functional modules in specific positions, creating a unique arrangement of the ARP module. EP400 interacts with the TRRAP subunit using a footprint that overlaps with that of the SAGA acetyltransferase complex, preventing the formation of a hybrid complex. Loss of the TRRAP subunit leads to mislocalization of NuA4/TIP60, resulting in the redistribution of H2A.Z and its acetylation across the genome, emphasizing the dual functionality of NuA4/TIP60 as a single macromolecular assembly.
Structural insights into the human NuA4/TIP60 acetyltransferase and chromatin remodeling complex.,Yang Z, Mameri A, Cattoglio C, Lachance C, Florez Ariza AJ, Luo J, Humbert J, Sudarshan D, Banerjea A, Galloy M, Fradet-Turcotte A, Lambert JP, Ranish JA, Cote J, Nogales E Science. 2024 Aug 1:eadl5816. doi: 10.1126/science.adl5816. PMID:39088653[26]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hawley SB, Tamura T, Miles LA. Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a. J Biol Chem. 2001 Jan 5;276(1):179-86. PMID:11027681 doi:http://dx.doi.org/10.1074/jbc.M004919200
- ↑ Gartner W, Rossbacher J, Zierhut B, Daneva T, Base W, Weissel M, Waldhausl W, Pasternack MS, Wagner L. The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis. Cell Motil Cytoskeleton. 2003 Oct;56(2):79-93. PMID:14506706 doi:http://dx.doi.org/10.1002/cm.10136
- ↑ Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, Kemler R, Pradel J. Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J. 2000 Nov 15;19(22):6121-30. PMID:11080158 doi:http://dx.doi.org/10.1093/emboj/19.22.6121
- ↑ Feng Y, Lee N, Fearon ER. TIP49 regulates beta-catenin-mediated neoplastic transformation and T-cell factor target gene induction via effects on chromatin remodeling. Cancer Res. 2003 Dec 15;63(24):8726-34. PMID:14695187
- ↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
- ↑ Hawley SB, Tamura T, Miles LA. Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a. J Biol Chem. 2001 Jan 5;276(1):179-86. PMID:11027681 doi:http://dx.doi.org/10.1074/jbc.M004919200
- ↑ Gartner W, Rossbacher J, Zierhut B, Daneva T, Base W, Weissel M, Waldhausl W, Pasternack MS, Wagner L. The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis. Cell Motil Cytoskeleton. 2003 Oct;56(2):79-93. PMID:14506706 doi:http://dx.doi.org/10.1002/cm.10136
- ↑ Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, Kemler R, Pradel J. Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J. 2000 Nov 15;19(22):6121-30. PMID:11080158 doi:http://dx.doi.org/10.1093/emboj/19.22.6121
- ↑ Feng Y, Lee N, Fearon ER. TIP49 regulates beta-catenin-mediated neoplastic transformation and T-cell factor target gene induction via effects on chromatin remodeling. Cancer Res. 2003 Dec 15;63(24):8726-34. PMID:14695187
- ↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
- ↑ Hawley SB, Tamura T, Miles LA. Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a. J Biol Chem. 2001 Jan 5;276(1):179-86. PMID:11027681 doi:http://dx.doi.org/10.1074/jbc.M004919200
- ↑ Gartner W, Rossbacher J, Zierhut B, Daneva T, Base W, Weissel M, Waldhausl W, Pasternack MS, Wagner L. The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis. Cell Motil Cytoskeleton. 2003 Oct;56(2):79-93. PMID:14506706 doi:http://dx.doi.org/10.1002/cm.10136
- ↑ Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, Kemler R, Pradel J. Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J. 2000 Nov 15;19(22):6121-30. PMID:11080158 doi:http://dx.doi.org/10.1093/emboj/19.22.6121
- ↑ Feng Y, Lee N, Fearon ER. TIP49 regulates beta-catenin-mediated neoplastic transformation and T-cell factor target gene induction via effects on chromatin remodeling. Cancer Res. 2003 Dec 15;63(24):8726-34. PMID:14695187
- ↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
- ↑ Hawley SB, Tamura T, Miles LA. Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a. J Biol Chem. 2001 Jan 5;276(1):179-86. PMID:11027681 doi:http://dx.doi.org/10.1074/jbc.M004919200
- ↑ Gartner W, Rossbacher J, Zierhut B, Daneva T, Base W, Weissel M, Waldhausl W, Pasternack MS, Wagner L. The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis. Cell Motil Cytoskeleton. 2003 Oct;56(2):79-93. PMID:14506706 doi:http://dx.doi.org/10.1002/cm.10136
- ↑ Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, Kemler R, Pradel J. Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J. 2000 Nov 15;19(22):6121-30. PMID:11080158 doi:http://dx.doi.org/10.1093/emboj/19.22.6121
- ↑ Feng Y, Lee N, Fearon ER. TIP49 regulates beta-catenin-mediated neoplastic transformation and T-cell factor target gene induction via effects on chromatin remodeling. Cancer Res. 2003 Dec 15;63(24):8726-34. PMID:14695187
- ↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
- ↑ Hawley SB, Tamura T, Miles LA. Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a. J Biol Chem. 2001 Jan 5;276(1):179-86. PMID:11027681 doi:http://dx.doi.org/10.1074/jbc.M004919200
- ↑ Gartner W, Rossbacher J, Zierhut B, Daneva T, Base W, Weissel M, Waldhausl W, Pasternack MS, Wagner L. The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis. Cell Motil Cytoskeleton. 2003 Oct;56(2):79-93. PMID:14506706 doi:http://dx.doi.org/10.1002/cm.10136
- ↑ Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, Kemler R, Pradel J. Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J. 2000 Nov 15;19(22):6121-30. PMID:11080158 doi:http://dx.doi.org/10.1093/emboj/19.22.6121
- ↑ Feng Y, Lee N, Fearon ER. TIP49 regulates beta-catenin-mediated neoplastic transformation and T-cell factor target gene induction via effects on chromatin remodeling. Cancer Res. 2003 Dec 15;63(24):8726-34. PMID:14695187
- ↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
- ↑ Yang Z, Mameri A, Cattoglio C, Lachance C, Florez Ariza AJ, Luo J, Humbert J, Sudarshan D, Banerjea A, Galloy M, Fradet-Turcotte A, Lambert JP, Ranish JA, Côté J, Nogales E. Structural insights into the human NuA4/TIP60 acetyltransferase and chromatin remodeling complex. Science. 2024 Aug 1:eadl5816. PMID:39088653 doi:10.1126/science.adl5816
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