EurekaMag.com logo
+ Site Statistics
References:
53,869,633
Abstracts:
29,686,251
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

RBX1 (RING box protein 1) E3 ubiquitin ligase is required for genomic integrity by modulating DNA replication licensing proteins



RBX1 (RING box protein 1) E3 ubiquitin ligase is required for genomic integrity by modulating DNA replication licensing proteins



Journal of Biological Chemistry 286(5): 3379-3386



RBX1 (RING box protein 1), also known as ROC1 (Regulator of Cullin 1), is an essential component of SCF (Skp1/Cullins/F-box) E3 ubiquitin ligases, which target diverse proteins for proteasome-mediated degradation. Our recent study showed that RBX1 silencing triggered a DNA damage response (DDR) leading to G(2)-M arrest, senescence, and apoptosis, with the mechanism remaining elusive. Here, we show that, in human cancer cells, RBX1 silencing causes the accumulation of DNA replication licensing proteins CDT1 and ORC1, leading to DNA double-strand breaks, DDR, G(2) arrest, and, eventually, aneuploidy. Whereas CHK1 activation by RBX1 silencing is responsible for the G(2) arrest, enhanced DNA damage renders cancer cells more sensitive to radiation. In Caenorhabditis elegans, RBX-1 silencing causes CDT-1 accumulation, triggering DDR in intestinal cells, which is largely abrogated by simultaneous CDT-1 silencing. RBX-1 silencing also induces lethality during development of embryos and in adulthood. Thus, RBX1 E3 ligase is essential for the maintenance of mammalian genome integrity and the proper development and viability in C. elegans.

(PDF emailed within 0-6 h: $19.90)

Accession: 055333702

Download citation: RISBibTeXText

PMID: 21115485

DOI: 10.1074/jbc.M110.188425



Related references

The poxviral RING protein p28 is a ubiquitin ligase that targets ubiquitin to viral replication factories. Journal of Virology 79(1): 597-601, 2004

RBX1/ROC1-SCF E3 ubiquitin ligase is required for mouse embryogenesis and cancer cell survival. Cell Division 4: 16-16, 2009

Arsenite Targets the RING Finger Domain of Rbx1 E3 Ubiquitin Ligase to Inhibit Proteasome-mediated Degradation of Nrf2. Chemical Research in Toxicology, 2018

Arabidopsis has two redundant Cullin3 proteins that are essential for embryo development and that interact with RBX1 and BTB proteins to form multisubunit E3 ubiquitin ligase complexes in vivo. Plant Cell 17(4): 1180-1195, 2005

CUL-4 ubiquitin ligase maintains genome stability by restraining DNA-replication licensing. Nature London 423(6942): 885-889, 2003

ASB2 is an Elongin BC-interacting protein that can assemble with Cullin 5 and Rbx1 to reconstitute an E3 ubiquitin ligase complex. Journal of Biological Chemistry 280(7): 5468-5474, 2004

The CRL4Cdt2 ubiquitin ligase targets the degradation of p21Cip1 to control replication licensing. Genes & Development 22(18): 2507-2519, 2008

Gid9, a second RING finger protein contributes to the ubiquitin ligase activity of the Gid complex required for catabolite degradation. Febs Letters 585(24): 3856-3861, 2012

Mammalian mediator subunit mMED8 is an Elongin BC-interacting protein that can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin ligase. Proceedings of the National Academy of Sciences of the United States of America 99(16): 10353-8, 2002

Muf1, a novel Elongin BC-interacting leucine-rich repeat protein that can assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase. Journal of Biological Chemistry 276(32): 29748-29753, 2001

Control of the Cdc6 replication licensing factor in metazoa - The role export and the CUL4 ubiquitin ligase. Cell Cycle 7(2): 146-150, 2008

Control of the Cdc6 replication licensing factor in metazoa: the role of nuclear export and the CUL4 ubiquitin ligase. Cell Cycle 7(2): 146-150, 2008

The ubiquitin-protein ligase Rsp5p is required to sort membrane proteins into multivesicular bodies. Yeast 20(Supplement 1): S39, July, 2003

Genomic organization and expression of the ubiquitin-proteasome complex-associated protein Rbx1/ROC1/Hrt1. Cellular and Molecular Biology 45(8): 1131-1137, 2000

The glomuvenous malformation protein Glomulin binds Rbx1 and regulates cullin RING ligase-mediated turnover of Fbw7. Molecular Cell 46(1): 67-78, 2012