SCFFbxo9 and CK2 direct the cellular response to growth factor withdrawal via Tel2/Tti1 degradation and promote survival in multiple myeloma
作者： Vanesa Fernández-Sáiz , Bianca-Sabrina Targosz , Simone Lemeer , Ruth Eichner , Christian Langer
DOI: 10.1038/NCB2651
关键词:
摘要: The Tel2 (also known as Telo2) and Tti1 proteins control the cellular abundance of mammalian PIKKs are integral components mTORC1 mTORC2. Here we report that targeted for degradation within by SCFFbxo9 ubiquitin ligase to adjust mTOR signalling growth factor availability. This process is primed CK2, which translocates cytoplasm mediate mTORC1-specific phosphorylation Tel2/Tti1, subsequent deprivation. As a consequence, inactivated restrain cell protein translation whereas relief feedback inhibition activates PI(3)K/TORC2/Akt pathway sustain survival. Significantly, primary human multiple myelomas exhibit high levels Fbxo9. In this setting, survival myeloma cells dependent on Fbxo9 expression. Thus, represents central regulatory mechanism with implications in myeloma, both promoting providing targets specific treatment
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sci-hub.se 参考文章(44)
Alexander Varshavsky, Three decades of studies to understand the functions of the ubiquitin family. Methods of Molecular Biology. ,vol. 832, pp. 1- 11 ,(2012) , 10.1007/978-1-61779-474-2_1
Birgitte B. Olsen, Barbara Guerra, Karsten Niefind, Olaf-Georg Issinger, Structural basis of the constitutive activity of protein kinase CK2. Methods in Enzymology. ,vol. 484, pp. 515- 529 ,(2010) , 10.1016/B978-0-12-381298-8.00025-3
J. H. Trembley, G. Wang, G. Unger, J. Slaton, K. Ahmed, CK2: A key player in cancer biology Cellular and Molecular Life Sciences. ,vol. 66, pp. 1858- 1867 ,(2009) , 10.1007/S00018-009-9154-Y
Florian Bassermann, David Frescas, Daniele Guardavaccaro, Luca Busino, Angelo Peschiaroli, Michele Pagano, The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA damage response checkpoint Cell. ,vol. 134, pp. 256- 267 ,(2008) , 10.1016/J.CELL.2008.05.043
N. V. Dorrello, A. Peschiaroli, D. Guardavaccaro, N. H. Colburn, N. E. Sherman, M. Pagano, S6K1- and ßTRCP-Mediated Degradation of PDCD4 Promotes Protein Translation and Cell Growth Science. ,vol. 314, pp. 467- 471 ,(2006) , 10.1126/SCIENCE.1130276
Michael J. Meredith, Rat hepatocytes prepared without collagenase: prolonged retention of differentiated characteristics in culture. Cell Biology and Toxicology. ,vol. 4, pp. 405- 425 ,(1988) , 10.1007/BF00117769
L. Busino, F. Bassermann, A. Maiolica, C. Lee, P. M. Nolan, S. I. H. Godinho, G. F. Draetta, M. Pagano, SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins Science. ,vol. 316, pp. 900- 904 ,(2007) , 10.1126/SCIENCE.1141194
Florian Bassermann, Christine von Klitzing, Silvia Münch, Ren-Yuan Bai, Hiroyuki Kawaguchi, Stephan W. Morris, Christian Peschel, Justus Duyster, NIPA Defines an SCF-Type Mammalian E3 Ligase that Regulates Mitotic Entry Cell. ,vol. 122, pp. 45- 57 ,(2005) , 10.1016/J.CELL.2005.04.034
F Bassermann, M Pagano, Dissecting the role of ubiquitylation in the DNA damage response checkpoint in G2. Cell Death & Differentiation. ,vol. 17, pp. 78- 85 ,(2010) , 10.1038/CDD.2009.104
Fenghuang Zhan, Bart Barlogie, Varant Arzoumanian, Yongsheng Huang, David R. Williams, Klaus Hollmig, Mauricio Pineda-Roman, Guido Tricot, Frits van Rhee, Maurizio Zangari, Madhav Dhodapkar, John D. Shaughnessy, Gene-expression signature of benign monoclonal gammopathy evident in multiple myeloma is linked to good prognosis. Blood. ,vol. 109, pp. 1692- 1700 ,(2006) , 10.1182/BLOOD-2006-07-037077