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.
Cell Div. 2009 Aug 6;4:16. doi: 10.1186/1747-1028-4-16.
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; 106:6203-6208Jia 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.
RBX1（也称为 ROC1）是 SCF（Skp1、Cullins、F-box 蛋白）E3 泛素连接酶的 RING 亚基，对于 SCF 引导各种底物的及时降解是必需的，从而在生理和病理条件下调节许多细胞过程。以前的研究表明，RBX1 对于酵母、秀丽隐杆线虫和果蝇的生长是必不可少的。RBX1 在小鼠发育和调节癌细胞存活中的作用尚不清楚。我们最近的工作表明，RBX1 是小鼠胚胎发生所必需的基因，并且 RBX1 的靶向缺失会导致 E7.5 时胚胎致死，这是由于 p27 积累导致的增殖减少。我们还表明，RBX1 在许多人类癌症中过度表达，并且 RBX1 的 siRNA 沉默会导致癌细胞死亡，这是由于连续诱导 G2-M 期阻滞、衰老和凋亡。这些发现揭示了 RBX1 在小鼠发育过程中的生理作用和人类癌细胞存活的病理作用。在 RBX1 缺失/沉默后，正常细胞（生长停滞）和癌细胞（细胞死亡）之间的不同结果表明 RBX1 是一个有效的抗癌靶点。
