QM, a Putative Tumor Suppressor, Regulates Proto-oncogene c-Yes

Oh, Hyung Suk; Kwon, Heejin; Sun, Suk Kyun; Yang, Chung-May

doi:10.1074/jbc.m201859200

Cited by 43 publications

(42 citation statements)

References 38 publications

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“…Some evidence indicates that RPL10/QM act as coactivators/repressors of transcription in human, Entamoeba histolytica, and chicken (Monteclaro and Vogt, 1993;Stanbridge et al, 1994;Chávez-Ríos et al, 2003). QM protein has also been shown to interact with the proto-oncogene c-Yes, a Src family kinase, and it can thus participate in signal transduction pathways in different intracellular processes, including cell stability, division, proliferation, migration, and differentiation (Oh et al, 2002). Thus, RPL10B and RPL10C genes are UV-B light regulated, so if they do not participate in translation under UV-B light, it is possible that extraribosomal activities of one or both proteins may be important under UV-B conditions.…”

Section: Discussionmentioning

confidence: 99%

Plant L10 Ribosomal Proteins Have Different Roles during Development and Translation under Ultraviolet-B Stress

et al. 2010

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(J.B., A.L.B.) Ribosomal protein L10 (RPL10) proteins are ubiquitous in the plant kingdom. Arabidopsis (Arabidopsis thaliana) has three RPL10 genes encoding RPL10A to RPL10C proteins, while two genes are present in the maize (Zea mays) genome (rpl10-1 and rpl10-2). Maize and Arabidopsis RPL10s are tissue-specific and developmentally regulated, showing high levels of expression in tissues with active cell division. Coimmunoprecipitation experiments indicate that RPL10s in Arabidopsis associate with translation proteins, demonstrating that it is a component of the 80S ribosome. Previously, ultraviolet-B (UV-B) exposure was shown to increase the expression of a number of maize ribosomal protein genes, including rpl10. In this work, we demonstrate that maize rpl10 genes are induced by UV-B while Arabidopsis RPL10s are differentially regulated by this radiation: RPL10A is not UV-B regulated, RPL10B is down-regulated, while RPL10C is up-regulated by UV-B in all organs studied. Characterization of Arabidopsis T-DNA insertional mutants indicates that RPL10 genes are not functionally equivalent. rpl10A and rpl10B mutant plants show different phenotypes: knockout rpl10A mutants are lethal, rpl10A heterozygous plants are deficient in translation under UV-B conditions, and knockdown homozygous rpl10B mutants show abnormal growth. Based on the results described here, RPL10 genes are not redundant and participate in development and translation under UV-B stress.

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Section: Discussionmentioning

confidence: 99%

Plant L10 Ribosomal Proteins Have Different Roles during Development and Translation under Ultraviolet-B Stress

et al. 2010

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“…Recent studies of mammalian cells suggest that QM is a key regulator for signaling pathways involving SH3 domain-containing membrane proteins, e.g., the Src family of kinases, since the QM protein directly interacts with the SH3 domain (37). Moreover, the yeast QM homologue, GRC5, is involved in translational control of gene expression in S. cerevisiae, based on the observation that GRC5 directly participates in the recombination of 60S and 40S ribosomal protein subunits (37). Several QM homologues have been identified in plants, but their physiological functions have not yet been described.…”

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confidence: 99%

Tomato QM-Like Protein Protects Saccharomyces cerevisiae Cells against Oxidative Stress by Regulating Intracellular Proline Levels

Chen¹,

Wanduragala

Becker

et al. 2006

Appl Environ Microbiol

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Exogenous proline can protect cells of Saccharomyces cerevisiae from oxidative stress. We altered intracellular proline levels by overexpressing the proline dehydrogenase gene (PUT1) of S. cerevisiae. Put1p performs the first enzymatic step of proline degradation in S. cerevisiae. Overexpression of Put1p results in low proline levels and hypersensitivity to oxidants, such as hydrogen peroxide and paraquat. A put1-disrupted yeast mutant deficient in Put1p activity has increased protection from oxidative stress and increased proline levels. Following a conditional life/death screen in yeast, we identified a tomato (Lycopersicon esculentum) gene encoding a QM-like protein (tQM) and found that stable expression of tQM in the Put1p-overexpressing strain conferred protection against oxidative damage from H 2 O 2 , paraquat, and heat. This protection was correlated with reactive oxygen species (ROS) reduction and increased proline accumulation. A yeast two-hybrid system assay was used to show that tQM physically interacts with Put1p in yeast, suggesting that tQM is directly involved in modulating proline levels. tQM also can rescue yeast from the lethality mediated by the mammalian proapoptotic protein Bax, through the inhibition of ROS generation. Our results suggest that tQM is a component of various stress response pathways and may function in proline-mediated stress tolerance in plants.Reactive oxygen species (ROS) are produced by all aerobically respiring cells. ROS can have detrimental effects on cells by oxidizing lipids, proteins, DNA, and carbohydrates, resulting in disease and death (22,47). It is therefore essential for aerobic organisms to modulate ROS levels and activities in order to protect against toxicity. The ␣-imino acid proline functions as a potent antioxidant by scavenging intracellular ROS generated by the phytopathogenic fungus Colletotrichum trifolii (7). The protective role of proline could be extended to the budding yeast Saccharomyces cerevisiae, since proline conferred cell survival in the presence of lethal levels of paraquat, a contact herbicide that uncouples electron transport by generating lethal levels of superoxide (7). Proline also is a wellknown osmoprotectant, capable of mitigating the impacts of drought, salt, and temperature stress in higher plants (11). In S. cerevisiae, the cryoprotective activity of proline was established through a positive correlation between intracellular proline levels and resistance to freeze stress (33). These abiotic stresses, including drought, salinity, and cold, are tightly linked to ROS generation (2). Thus, these findings suggest a positive correlation between intracellular proline levels and resistance to oxidative stress. However, the mechanisms of proline-mediated stress protection and, in particular, the components involved in proline-dependent signal transduction pathways are still not well understood.Intracellular proline levels are controlled by a series of key proline metabolic enzymes mediating proline synthesis and degradation. In S. cer...

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“…17 Third, QM has been shown to interact with several Src family kinases such as c-Yes, and thus may participate in signal transduction of these kinases in many intracellular functions, including cell stability, division, proliferation, migration and differentiation. 18 QM protein may regulate cell proliferation, differentiation and apoptosis through one or all of these functions, that is, regulation of transcription, protein synthesis, signal transduction and/or other unknown mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Reduction of QM protein expression correlates with tumor grade in prostatic adenocarcinoma

Altınok

Powell

Che

et al. 2005

Prostate Cancer Prostatic Dis

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The QM protein is a transcription cofactor inhibiting the activity of AP-1 transcription factors and is also a ribosomal protein participating in protein synthesis. While protein synthesis is known to be increased in many cancers, inhibition of AP-1 activity presumably suppresses development and growth of sex-hormone-regulated tumor cells. The present study is the first report on immunohistochemical data of QM in human prostatic tissues. Paraffin sections of human prostate cancer samples were immunohistochemically stained for QM. The staining scores were analyzed with the clinicopathologic data of the patients. QM protein expression was found in all normal prostate glands adjacent to prostate cancer and in various intraepithelial neoplasia (PIN). In prostate cancer, the staining intensity and stained areas were decreased, compared to the normal glands and PIN lesions; in high-grade tumors only some patches of tumor cells showed positivity. Intense (3 þ ) staining was mostly observed in the Gleason grade three areas (48%) compared to grade 4 and 5 areas (22%), although both low and high-grade tumors showed similar percentages of weakly stained areas. Moreover, staining in prostatic adenocarcinoma was often topographically patchy and varied from negative or weak (1 þ ) to intense (3 þ ). There was an inverse correlation from normal to low-grade tumors and then to high-grade tumors. However, in high-grade tumors, the positive areas were mostly confined to peripheral aspects of tumors and were particularly strong in foci of perineural invasion. This preliminary study suggests that decreased QM expression may be associated with early development of prostate cancer, but later a high level of QM may facilitate progression of the tumors to a more aggressive phenotype.

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QM, a Putative Tumor Suppressor, Regulates Proto-oncogene c-Yes

Abstract: The QM gene encodes a 24.5 kDa ribosomal protein L10 known to be highly homologous to a Jun-binding protein (

Cited by 43 publications

References 38 publications

Plant L10 Ribosomal Proteins Have Different Roles during Development and Translation under Ultraviolet-B Stress

Plant L10 Ribosomal Proteins Have Different Roles during Development and Translation under Ultraviolet-B Stress

Tomato QM-Like Protein Protects Saccharomyces cerevisiae Cells against Oxidative Stress by Regulating Intracellular Proline Levels

Reduction of QM protein expression correlates with tumor grade in prostatic adenocarcinoma

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