The yeast growth control gene GRC5 is highly homologous to the mammalian putative tumor suppressor gene QM

Koller, Hannelore T.; Klade, Torsten; Ellinger, Adolf; Breitenbach, Michael

doi:10.1002/(sici)1097-0061(199601)12:1<53::aid-yea886>3.0.co;2-m

Cited by 38 publications

(39 citation statements)

References 36 publications

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Section: Discussionmentioning

confidence: 99%

“…This "growth control" gene was named GRC5 (35). The grc5-1 temperaturesensitive yeast mutant (35), which is rescued by QSR1, accumulates cell wall material at the septum, exhibits an aberrant actin cytoskeleton, and is not viable on rich media. Given that these defects seem distantly related and were observed 24 h after a shift to restrictive temperature, they could be pleiotropic effects secondary to a lesion in this ribosomal protein, affecting protein synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…Rates of protein synthesis are diminished in cell-free extracts from qsr1-1 mutant cells. Extracts from yeast strains MMY3-3A (QSR1) and MMY3-3B (qsr1-1) were treated with nuclease and assayed for 35 S incorporation into trichloroacetic acid-insoluble material with or without addition of poly(A) ϩ RNA.…”

Section: Discussionmentioning

confidence: 99%

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QSR1, an Essential Yeast Gene with a Genetic Relationship to a Subunit of the Mitochondrial Cytochromebc 1 Complex, Codes for a 60 S Ribosomal Subunit Protein

Dick¹,

Karamanou²,

Trumpower

1997

Journal of Biological Chemistry

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QSR1 (quinol-cytochrome c reductase subunit-requiring) is a highly conserved, essential gene in Saccharomyces cerevisiae that was identified through a synthetic lethal screen by its genetic relationship to QCR6, the gene for subunit 6 (Qcr6p) of the mitochondrial cytochrome bc 1 complex. The function of the QSR1-encoded protein (Qsr1p) and its relationship to the QCR6-encoded protein are unknown.When yeast cell lysates are fractionated by density gradient centrifugation, Qsr1p separates from organelles and sediments with a uniformly sized population of particles that are similar to eukaryotic ribosomes upon velocity gradient centrifugation. When 40 S and 60 S ribosomal subunits are separated on velocity gradients, Qsr1p is found exclusively with the 60 S subunits, where it is a stoichiometric component. Extracts prepared from qsr1-1 cells are defective in in vitro translation assays relative to the wild type.In yeast cell lysates in which QCR6 rescues an otherwise lethal qsr1-1 mutation, Qcr6p is found only in mitochondria, both in respiratory-competent cells and in rho 0 cells in which the bc 1 complex is no longer present. These results suggest that suppression of the qsr1-1 mutation by QCR6 occurs by a trans-relationship across the outer mitochondrial membrane.All cytochrome bc 1 complexes contain three redox proteins, cytochrome b, cytochrome c 1 , and an iron-sulfur protein, which are essential for the electron transfer and energy transduction functions of this enzyme in respiration and photosynthesis (1). The cytochrome bc 1 complexes of mitochondria also contain seven or eight additional subunits that lack prosthetic groups and that are not present in the bc 1 complexes of prokaryotes (2). The functions of these supernumerary subunits in the mitochondrial enzymes are largely unknown.QCR6 is the nuclear encoded gene for subunit 6 (Qcr6p) of the mitochondrial cytochrome bc 1 complex. Deletion of QCR6 does not impair growth of yeast on respiratory substrates at temperatures up to 35°C, indicating that the supernumerary subunit 6 is not essential for respiration, although the deletion does result in a temperature-sensitive petite phenotype at 37°C (3). To test whether the deletion of QCR6 might be covered by another, functionally redundant gene, we screened for mutants that require the nonessential subunit 6 and identified quinol-cytochrome c reductase subunit-requiring mutants in two complementation groups, which we named qsr1 and qsr2 (4). Surprisingly, the qsr mutants require QCR6 to grow on either fermentable or nonfermentable carbon sources. This suggests that subunit 6 of the cytochrome bc 1 complex has a role outside of respiration.QCR6 suppresses an otherwise lethal missense mutation in a qsr1-1 mutant. We cloned QSR1 by complementing the qsr1-1 mutant for growth in the absence of QCR6 and showed that QSR1 is an essential gene in yeast (4). The protein encoded by QSR1 is highly conserved and has been identified in at least 10 different eukaryotic organisms (4 -10). Comparisons of the amino acid sequen...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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QSR1, an Essential Yeast Gene with a Genetic Relationship to a Subunit of the Mitochondrial Cytochromebc 1 Complex, Codes for a 60 S Ribosomal Subunit Protein

Dick¹,

Karamanou²,

Trumpower

1997

Journal of Biological Chemistry

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“…Yeast strain LK41-2B harbors the temperature-sensitive (ts) RPL10[G161D] mutation, originally called grc5-1 ts (growth control) 25 and yeast strains LK41-22C and YLG 499 (EUROSCARF strain BY4742a, EUROSCARF: http://www.uni-frankfurt.de/fb15/mikro/euroscarf) served as wild-type (WT) controls. The plasmids used in this study are listed in Table 2 and the yeast strains employed in this study are listed in Table 3.…”

Section: Yeast Growth Conditions Yeast Strains and Plasmidsmentioning

confidence: 99%

Mutations in the ribosomal protein gene RPL10 suggest a novel modulating disease mechanism for autism

et al. 2006

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Autism has a strong genetic background with a higher frequency of affected males suggesting involvement of X-linked genes and possibly also other factors causing the unbalanced sex ratio in the etiology of the disorder. We have identified two missense mutations in the ribosomal protein gene RPL10 located in Xq28 in two independent families with autism. We have obtained evidence that the amino-acid substitutions L206M and H213Q at the C-terminal end of RPL10 confer hypomorphism with respect to the regulation of the translation process while keeping the basic translation functions intact. This suggests the contribution of a novel, possibly modulating aberrant cellular function operative in autism. Previously, we detected high expression of RPL10 by RNA in situ hybridization in mouse hippocampus, a constituent of the brain limbic system known to be afflicted in autism. Based on these findings, we present a model for autistic disorder where a change in translational function is suggested to impact on those cognitive functions that are mediated through the limbic system.

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“…14 Although in yeast lack of QM proves lethal. 15,16 QM seems to be dispensable in certain cells with high protein synthetic rate, since its expression is not detectable in some cells such as hematopoietic cells and bone marrow cells in adult mice. 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.…”

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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The yeast growth control gene GRC5 is highly homologous to the mammalian putative tumor suppressor gene QM

Cited by 38 publications

References 36 publications

QSR1, an Essential Yeast Gene with a Genetic Relationship to a Subunit of the Mitochondrial Cytochromebc 1 Complex, Codes for a 60 S Ribosomal Subunit Protein

QSR1, an Essential Yeast Gene with a Genetic Relationship to a Subunit of the Mitochondrial Cytochromebc 1 Complex, Codes for a 60 S Ribosomal Subunit Protein

Mutations in the ribosomal protein gene RPL10 suggest a novel modulating disease mechanism for autism

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

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