Taxonomic distribution of proteins containing Romo1 domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing Romo1 domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Replicative senescence induced by Romo1-derived reactive oxygen species.

Chung YM, Lee SB, Kim HJ, Park SH, Kim JJ, Chung JS, Yoo YD
J Biol Chem. 2008; 283: 33763-71

Persistent accumulation of DNA damage induced by reactive oxygen species (ROS) isproposed to be a major contributor toward the aging process. Furthermore, anincrease in age-associated ROS is strongly correlated with aging in variousspecies, including humans. Here we showed that the enforced expression of the ROSmodulator 1 (Romo1) triggered premature senescence by ROS production, and thisalso contributed toward induction of DNA damage. Romo1-derived ROS was found tooriginate in the mitochondrial electron transport chain. Romo1 expressiongradually increased in proportion to population doublings of IMR-90 humanfibroblasts. An increase in ROS production in these cells with high populationdoubling was blocked by the Romo1 knockdown using Romo1 small interfering RNA.Romo1 knockdown also inhibited the progression of replicative senescence. Basedon these results, we suggest that age-related ROS levels increase, and thiscontributes to replicative senescence, which is directly associated with Romo1expression.

A critical role for Romo1-derived ROS in cell proliferation.

Na AR, Chung YM, Lee SB, Park SH, Lee MS, Yoo YD
Biochem Biophys Res Commun. 2008; 369: 672-8

Low levels of endogenous reactive oxygen species (ROS) originating from NADPHoxidase have been implicated in various signaling pathways induced by growthfactors and mediated by cytokines. However, the main source of ROS is known to bethe mitochondria, and increased levels of ROS from the mitochondria have beenobserved in many cancer cells. Thus far, the mechanism of ROS production incancer cell proliferation in the mitochondria is not well-understood. We recentlyidentified a novel protein, ROS modulator 1 (Romo1), and reported that increased expression of Romo1-triggered ROS production in the mitochondria. The experimentsconducted in the present study showed that Romo1-derived ROS were indispensablefor the proliferation of both normal and cancer cells. Furthermore, whilst cellgrowth was inhibited by blocking the ERK pathway in cells transfected with siRNA directed against Romo1, the cell growth was recovered by addition of exogenoushydrogen peroxide. The results of this study suggest that Romo1-induced ROS mayplay an important role in redox signaling in cancer cells.

Drug resistance to 5-FU linked to reactive oxygen species modulator 1.

Hwang IT, Chung YM, Kim JJ, Chung JS, Kim BS, Kim HJ, Kim JS, Yoo YD
Biochem Biophys Res Commun. 2007; 359: 304-10

While acute oxidative stress triggers cell apoptosis or necrosis, persistentoxidative stress induces genomic instability and has been implicated in tumorprogression and drug resistance. In a previous report, we demonstrated thatreactive oxygen species modulator 1 (Romo1) expression was up-regulated in mostcancer cell lines and suggested that increased Romo1 expression might conferchronic oxidative stress to tumor cells. In this study, we show that enforcedRomo1 expression induces reactive oxygen species (ROS) production in themitochondria leading to massive cell death. However, tumor cells that adapt tooxidative stress by increasing manganese superoxide dismutase (MnSOD), Prx I, andBcl-2 showed drug resistance to 5-FU. To elucidate the relationship between5-FU-induced ROS production and Romo1 expression, Romo1 siRNA was used to inhibit5-FU-triggered Romo1 induction. Romo1 siRNA treatment efficiently blocked5-FU-induced ROS generation, demonstrating that 5-FU treatment stimulated ROSproduction through Romo1 induction. Based on these results we suggest thatcellular adaptive response to Romo1-induced ROS is another mechanism of drugresistance to 5-FU and Romo1 expression may provide a new clinical implication indrug resistance of cancer chemotherapy.

A novel protein, Romo1, induces ROS production in the mitochondria.

Chung YM, Kim JS, Yoo YD
Biochem Biophys Res Commun. 2006; 347: 649-55

The majority of endogenous reactive oxygen species (ROS) are produced in themitochondrial respiratory chain. An imbalance in ROS production alters theintracellular redox homeostasis, triggers DNA damage, and contributes to cancerdevelopment and progression. This study identified a novel protein, reactiveoxygen species modulator 1 (Romo1), which is localized in the mitochondria. Romo1was found to increase the level of ROS in the cells. Increased Romo1 expressionwas observed in various cancer cell lines. This suggests that the increased Romo1expression during cancer progression may cause persistent oxidative stress totumor cells, which can increase their malignancy.