| 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
Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that degrades aberrant mRNAs and also regulates the expression of a wide range of physiological transcripts. RUVBL1 and RUVBL2 AAA-ATPases form an hetero-hexameric ring that is part of several macromolecular complexes such as INO80, SWR1 and R2TP. Interestingly, RUVBL1-RUVBL2 ATPase activity is required for NMD activation by an unknown mechanism. Here, we show that DHX34, an RNA helicase regulating NMD initiation, directly interacts with RUVBL1-RUVBL2 in vitro and in cells. Cryo-EM reveals that DHX34 induces extensive changes in the N-termini of every RUVBL2 subunit in the complex, stabilizing a conformation that does not bind nucleotide and thereby down-regulates ATP hydrolysis of the complex. Using ATPase-deficient mutants, we find that DHX34 acts exclusively on the RUVBL2 subunits. We propose a model, where DHX34 acts to couple RUVBL1-RUVBL2 ATPase activity to the assembly of factors required to initiate the NMD response.
Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA decay factor DHX34, as evidenced by Cryo-EM.,Lopez-Perrote A, Hug N, Gonzalez-Corpas A, Rodriguez CF, Serna M, Garcia-Martin C, Boskovic J, Fernandez-Leiro R, Caceres JF, Llorca O Elife. 2020 Nov 18;9. pii: 63042. doi: 10.7554/eLife.63042. PMID:33205750[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
- ↑ López-Perrote A, Hug N, González-Corpas A, Rodríguez CF, Serna M, García-Martín C, Boskovic J, Fernandez-Leiro R, Caceres JF, Llorca O. Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA decay factor DHX34, as evidenced by Cryo-EM. Elife. 2020 Nov 18;9:e63042. PMID:33205750 doi:10.7554/eLife.63042
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