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Sci. Signal., 6 April 2010
Vol. 3, Issue 116, p. ra27
[DOI: 10.1126/scisignal.2000468]


Editor's Summary

Masters of Integrity
In order to survive and faithfully reproduce, cells must not only maintain the integrity of their genome but also regulate the expression of the encoded products, ensure the quality of the transcripts, and coordinate protein production with metabolic status. Members of the phosphatidylinositol 3-kinase–related protein kinase (PIKK) family play essential roles in the DNA- and RNA-based processes that ensure genome integrity and accurate gene expression. Izumi et al. show that the two members of the AAA+ family of proteins, RUVBL1 and RUVBL2, which form a complex involved in chromatin-based processes, also regulated the activity and abundance of all members of the PIKK family. Furthermore, through an interaction with the PIKK member SMG-1, RUVBL1 and RUVBL2 contributed to the formation of macromolecular complexes involved in nonsense-mediated decay, a process by which prematurely terminated mRNA transcripts are eliminated to ensure that potentially dangerous truncated proteins are not produced.

Citation: N. Izumi, A. Yamashita, A. Iwamatsu, R. Kurata, H. Nakamura, B. Saari, H. Hirano, P. Anderson, S. Ohno, AAA+ Proteins RUVBL1 and RUVBL2 Coordinate PIKK Activity and Function in Nonsense-Mediated mRNA Decay. Sci. Signal. 3, ra27 (2010).

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Structural and functional analysis of the three MIF4G domains of nonsense-mediated decay factor UPF2.
M. Clerici, A. Deniaud, V. Boehm, N. H. Gehring, C. Schaffitzel, and S. Cusack (2014)
Nucleic Acids Res. 42, 2673-2686
   Abstract »    Full Text »    PDF »
Inhibition of SMG-8, a subunit of SMG-1 kinase, ameliorates nonsense-mediated mRNA decay-exacerbated mutant phenotypes without cytotoxicity.
F. Usuki, A. Yamashita, T. Shiraishi, A. Shiga, O. Onodera, I. Higuchi, and S. Ohno (2013)
PNAS 110, 15037-15042
   Abstract »    Full Text »    PDF »
Chaperone-like activity of the AAA+ proteins Rvb1 and Rvb2 in the assembly of various complexes.
N. Nano and W. A. Houry (2013)
Phil Trans R Soc B 368, 20110399
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The Emergence of the Conserved AAA+ ATPases Pontin and Reptin on the Signaling Landscape.
J. Rosenbaum, S. H. Baek, A. Dutta, W. A. Houry, O. Huber, T. R. Hupp, and P. M. Matias (2013)
Science Signaling 6, mr1
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The ATPase Activity of Reptin Is Required for Its Effects on Tumor Cell Growth and Viability in Hepatocellular Carcinoma.
A. Grigoletto, V. Neaud, N. Allain-Courtois, P. Lestienne, and J. Rosenbaum (2013)
Mol. Cancer Res. 11, 133-139
   Abstract »    Full Text »    PDF »
Conformational transitions regulate the exposure of a DNA-binding domain in the RuvBL1-RuvBL2 complex.
A. Lopez-Perrote, H. Munoz-Hernandez, D. Gil, and O. Llorca (2012)
Nucleic Acids Res. 40, 11086-11099
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Ubiquitin-specific Peptidase 9, X-linked (USP9X) Modulates Activity of Mammalian Target of Rapamycin (mTOR).
P. Agrawal, Y.-T. Chen, B. Schilling, B. W. Gibson, and R. E. Hughes (2012)
J. Biol. Chem. 287, 21164-21175
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Vitrification at the pre-antral stage transiently alters inner mitochondrial membrane potential but proteome of in vitro grown and matured mouse oocytes appears unaffected.
M. Demant, T. Trapphoff, T. Frohlich, G. J. Arnold, and U. Eichenlaub-Ritter (2012)
Hum. Reprod. 27, 1096-1111
   Abstract »    Full Text »    PDF »
N- and C-terminal Upf1 phosphorylations create binding platforms for SMG-6 and SMG-5:SMG-7 during NMD.
Y. Okada-Katsuhata, A. Yamashita, K. Kutsuzawa, N. Izumi, F. Hirahara, and S. Ohno (2012)
Nucleic Acids Res. 40, 1251-1266
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The nonsense-mediated mRNA decay SMG-1 kinase is regulated by large-scale conformational changes controlled by SMG-8.
E. Arias-Palomo, A. Yamashita, I. S. Fernandez, R. Nunez-Ramirez, Y. Bamba, N. Izumi, S. Ohno, and O. Llorca (2011)
Genes & Dev. 25, 153-164
   Abstract »    Full Text »    PDF »
Characterization of SMG-9, an essential component of the nonsense-mediated mRNA decay SMG1C complex.
I. S. Fernandez, A. Yamashita, E. Arias-Palomo, Y. Bamba, R. A. Bartolome, M. A. Canales, J. Teixido, S. Ohno, and O. Llorca (2011)
Nucleic Acids Res. 39, 347-358
   Abstract »    Full Text »    PDF »
Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes.
H. Takai, Y. Xie, T. de Lange, and N. P. Pavletich (2010)
Genes & Dev. 24, 2019-2030
   Abstract »    Full Text »    PDF »
Tti1 and Tel2 Are Critical Factors in Mammalian Target of Rapamycin Complex Assembly.
T. Kaizuka, T. Hara, N. Oshiro, U. Kikkawa, K. Yonezawa, K. Takehana, S.-i. Iemura, T. Natsume, and N. Mizushima (2010)
J. Biol. Chem. 285, 20109-20116
   Abstract »    Full Text »    PDF »

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