Overexpression of DRG2 Increases G2/M Phase Cells and Decreases Sensitivity to Nocodazole-Induced Apoptosis

Song, Hebok; Kim, Sin-Il; Ko, Myoung Seok; Kim, Hyo Jeong; Heo, Jin Chul; Lee, Hae Jin; Lee, Han Saem; Han, In Seob; Kwack, KyuBum; Park, Jeong Woo

doi:10.1093/jb/mvh040

Cited by 30 publications

(30 citation statements)

References 17 publications

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“…DRG1 and DRG2 comprise a highly conserved subfamily of GTP-binding proteins thought to regulate cell growth [18, 19]. In the present study, we demonstrated that ZC3H15, which interacts with DRG1, is highly expressed in HCC and regulates tumor cell proliferation in vitro and in vivo .…”

Section: Discussionsupporting

confidence: 61%

Elevated ZC3H15 increases HCC growth and predicts poor survival after surgical resection

et al. 2016

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Zinc finger CCCH-type containing 15 (ZC3H15), also known as DRG family regulatory protein 1 (DFRP1), is a highly conserved eukaryotic protein that associates with active translation machinery. The aim of our study was to explore the clinical relevance and intrinsic functions of ZC3H15 in hepatocellular carcinoma (HCC). We constructed a cohort with 261 tumor and matched normal tissues from HCC patients. ZC3H15 protein and mRNA levels were determined using immunohistochemistry, western blot analysis, and quantitative polymerase chain reaction. ZC3H15 was highly expressed in the majority of HCC cases, and high ZC3H15 levels were significantly associated with high serum a-fetoprotein (AFP) levels (>20 ng/mL) and vascular invasion. Kaplan-Meier and Cox regression data indicated that elevated ZC3H15 was an independent predictor for HCC-specific disease-free survival (hazards ratio [HR], 1.789; 95% confidence interval [95% CI], 1.298-2.466 [P=0.0004]) and overall survival (HR, 1.613; 95% CI, 1.120-2.322 [P=0.0101]). Interaction of ZC3H15 with TRAF2 increased activation of NFκB signaling. These results suggest ZC3H15 is an independent prognostic marker in HCC patients that is clinicopathologically associated with tumor invasion and serum AFP levels.

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Section: Discussionsupporting

confidence: 61%

Elevated ZC3H15 increases HCC growth and predicts poor survival after surgical resection

et al. 2016

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“…5A). DRG1 has been implicated in regulation of the cell cycle and may be important in growth and differentiation of cells (76).…”

Section: Genes Associated With Cell Cycle Control and Myoblast Prolifmentioning

confidence: 99%

Discovery and characterization of nutritionally regulated genes associated with muscle growth in Atlantic salmon

Bower

Johnston

2010

Physiological Genomics

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“…Conversely, DRG2 is found to be highly expressed in actively growing tissues and the reproductive organs of Arabidopsis thaliana (mouse-ear cress) (8). Moreover, overexpression of DRG2 caused cell cycle arrest in the G2/M phase (19,32). Collectively, these findings suggest that DRG2 may affect differentiation and activity of OCs.…”

mentioning

confidence: 69%

“…Previous reports suggest that DRG2 plays a critical role in the growth and differentiation of cells (19,32). It is possible that DRG2 modulates the differentiation of OCs, leading to the increased bone resorption and loss observed in the Tg mice.…”

Section: Discussionmentioning

confidence: 96%

Overexpression of developmentally regulated GTP-binding protein-2 increases bone loss

Sul

Kim

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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The developmentally regulated GTP-binding protein-2 (DRG2) is a novel subclass of GTPbinding proteins. Many functional characteristics of osteoclasts (OC) are associated with small GTPases. We hypothesized that DRG2 affects bone mass via modulating OC activity. Using DRG2 transgenic mice, we investigated the role of DRG2 in bone remodeling. DRG2 overexpression caused a decrease in bone mass and an increase in the number and activity of OC in vivo. DRG2 overexpression increased fusion, spreading, survival, and resorption activity of OC in vitro. Downregulation of DRG2 by siRNA decreased fusion, spreading, and survival of OC, supporting the observations found in DRG2 transgenic OC. Transgenic mature OCs were larger, with actin rings and higher ERK, Akt, Rac1 and Rho activities than wild-type OCs. Inhibition of these proteins abolished the effects of DRG2 on formation of large OCs with actin rings, implying that DRG2 affects cytoskeleton reorganization in a Rac1/Rho/ERK/Akt-dependent manner. In summary, DRG2 is associated with survival and cytoskeleton organization of OC under influence of macrophage colony-stimulating factor, and its overexpression leads to elevated bone resorptive activity of OC, resulting in bone loss. DRG2; osteoclast; fusion; spreading; bone resorption BONE UNDERGOES DYNAMIC REMODELING, and maintenance of bone mass and integrity requires a precise balance between bone resorption by osteoclasts (OC) and bone formation by osteoblasts. In osteoporosis, resorption exceeds formation, whereas osteopetrosis is due to defective OC formation and function. OC differentiation depends on at least two factors derived from stromal cells/osteoblasts: macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-B ligand (RANKL) (3, 12). During differentiation, OCs become multinucleated by fusion, which plays a critical role in bone resorption (13). To actively resorb bone, OC forms an actin ring that is a complex molecular attachment structure that seals off an extracellular compartment located between the cell and resorbing bone (5). By virtue of tight sealing, the extracellular compartment is characterized by maintaining a low pH and enriching lysosomal enzymes that are required for digestion of the bone matrix.Many OC properties that are necessary for efficient bone resorption, such as actin ring formation, fusion, and cell survival, depend on the activity of small GTPases (6,15,16,36). The Rho family of GTPases plays a critical role in actin organization, with RhoA, Rac1, Cdc42, and RhoU being responsible for cytoskeletal organization and the polarization of OCs (6, 15, 36). The ARF GTPase family, known to regulate membrane trafficking and actin dynamics, is responsible for the regulation of the OC cytoskeleton and formation of the sealing zone (11). Decrease in Rac2 impairs migration and fusion required for OC and results in bone defects found in Shwachman-Diamond syndrome (24). The activity of Rac1 (9) and Ras (4) is essential for OC survival. Although several small GTPases have...

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Overexpression of DRG2 Increases G2/M Phase Cells and Decreases Sensitivity to Nocodazole-Induced Apoptosis

Cited by 30 publications

References 17 publications

Elevated ZC3H15 increases HCC growth and predicts poor survival after surgical resection

Elevated ZC3H15 increases HCC growth and predicts poor survival after surgical resection

Discovery and characterization of nutritionally regulated genes associated with muscle growth in Atlantic salmon

Overexpression of developmentally regulated GTP-binding protein-2 increases bone loss

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