RBX1/ROC1-SCF E3 ubiquitin ligase is required for mouse embryogenesis and cancer cell survival
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BioMed Central
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Commentary
RBX1/ROC1-SCF E3 ubiquitin ligase is required for mouse embryogenesis and cancer cell survival Lijun Jia and Yi Sun* Address: Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, 4424B Medical Science-I, 1301 Catherine Street, Ann Arbor, MI 48109, USA Email: Lijun Jia - [email protected]; Yi Sun* - [email protected] * Corresponding author
Published: 6 August 2009 Cell Division 2009, 4:16
doi:10.1186/1747-1028-4-16
Received: 24 July 2009 Accepted: 6 August 2009
This article is available from: http://www.celldiv.com/content/4/1/16 © 2009 Jia and Sun; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract RBX1 (also known as ROC1) is a RING subunit of SCF (Skp1, Cullins, F-box proteins) E3 ubiquitin ligases, required for SCF to direct a timely degradation of diverse substrates, thereby regulating numerous cellular processes under both physiological and pathological conditions. Previous studies have shown that RBX1 is essential for growth in yeast, Caenorhabditis elegans and Drosophila. The role of RBX1 in mouse development and in regulation of cancer cell survival was unknown. Our recent work demonstrated that RBX1 is an essential gene for mouse embryogenesis, and targeted disruption of RBX1 causes embryonic lethality at E7.5 due to hypoproliferation as a result of p27 accumulation. We also showed that RBX1 is overexpressed in a number of human cancers, and siRNA silencing of RBX1 caused cancer cell death as a result of sequential induction of G2-M arrest, senescence and apoptosis. These findings reveal a physiological role of RBX1 during mouse development and a pathological role for the survival of human cancer cells. Differential outcomes between normal (growth arrest) and cancer cells (cell death) upon RBX1 disruption/silencing suggest RBX1 as a valid anticancer target. Comments on: Tan M, Davis SW, Saunders TL, Zhu Y, Sun Y. RBX1/ROC1 disruption results in early embryonic lethality due to proliferation failure, partially rescued by simultaneous loss of p27. Proc Natl Acad Sci USA. 2009; 106:6203–6208 Jia L, Soengas MS, Sun Y. ROC1/RBX1 E3 ubiquitin ligase silencing suppresses tumor cell growth via sequential induction of G2-M arrest, apoptosis, and senescence. Cancer Res. 2009; 69:4974–82
Introduction SCF (Skp1, Cullins, F-box proteins) E3 ubiquitin ligases, consist of Skp1, Cullins, F-box proteins, and the RING domain containing protein RBX1/ROC1 or its family member RBX2/ROC2/SAG. By promoting degradation of many short-lived proteins, including cell cycle regulators, transcription factors and signal transducers, RBX1-SCF E3
ligases regulate many biological processes. As an essential subunit of the SCF E3 ligase complex, RBX1, is evolutionari
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