Disease relevance of RPL10

• QM is a human cDNA originally isolated as a transcript elevated in a nontumorigenic Wilms' tumor microcell hybrid, relative to the tumorigenic parental cell line [1].
• Taken together, these results suggest that the RP-L10 may positively regulate the GDNF/Ret-mediated signaling of neurite outgrowth in the neuroblastoma cell line, SH-SY-5y [2].
• Paraffin sections of human prostate cancer samples were immunohistochemically stained for QM [3].
• Reduction of QM protein expression correlates with tumor grade in prostatic adenocarcinoma [3].
• P0 may, therefore, be the eukaryotic equivalent of Escherichia coli ribosomal protein L10 [4].

High impact information on RPL10

• The median number of days with an absolute neutrophil count (ANC) less than 100/microL and platelet count less than 20,000/microL were 8 and 3, respectively, after NOV plus L-PAM, and 7 and 4, respectively, after VP-16 plus PP [5].
• We have found that two different regions of QM protein were associated with the SH3 domain of c-Yes [6].
• QM, a putative tumor suppressor, regulates proto-oncogene c-yes [6].
• These results suggest that the QM protein might be a regulator for various signal transduction pathways involving SH3 domain-containing membrane proteins [6].
• Immunofluorescence studies showed that the QM proteins and c-Yes are able to interact in various tumor cell lines in vivo [6].

Chemical compound and disease context of RPL10

• Amino acid sequence of the FV region of a human monoclonal IgM (NOV) with specificity for the capsular polysaccharide of the group B meningococcus and of Escherichia coli K1, which cross-reacts with polynucleotides and with denatured DNA [7].
• The implications of the o-quinone/QM pathway for the in vivo effects of catechol estrogens are not known; however, given the direct link between excessive exposure to endogenous estrogens and the enhanced risk of breast cancer, the potential for formation of additional reactive intermediates needs to be explored [8].
• The optimal use of mitoxantrone (NOV) in the high-dose range requires elucidation of its maximum tolerated dose with peripheral blood progenitor cell (PBPC) support and the time interval needed between drug administration and PBPC reinfusion in order to avoid graft toxicity [9].
• Three cohorts of ten patients with breast cancer (BC) or non-Hodgkin's lymphoma (NHL) received escalating doses of NOV, 60, 75 and 90 mg m(-2) plus melphalan (L-PAM), 140-180 mg m(-2), with PBPC rescue 96 h after NOV. Haematological toxicity was evaluated daily (WHO criteria) [9].
• These results substantiate the conclusion that the involvement of the o-quinone/ QM pathway in catechol toxicity depends on a combination between the rate of enzymatic formation of the o-quinone, the rate of isomerization to the more electrophilic QM, and the chemical reactivity of the quinoids [10].

Biological context of RPL10

• We have identified two missense mutations in the ribosomal protein gene RPL10 located in Xq28 in two independent families with autism [11].
• 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 [11].
• The QM mRNA level is modulated between the tumorigenic and nontumorigenic cell lines and therefore may be involved in the maintenance of the nontumorigenic phenotype [12].
• The QM transcript is expressed in a wide variety of embryonic and adult tissues and demonstrates a down regulation of expression in adult kidney and heart [12].
• A subtractive cDNA/RNA hybridization performed between the tumorigenic parent (G401) and a nontumorigenic microcell hybrid of G401 (110.1/G401.1) containing the der(11) chromosome resulted in the identification of a single novel cDNA clone, designated QM [12].

Anatomical context of RPL10

• 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 [11].
• In agreement with this, QM was found to copurify with the ribosome complex [1].
• Subcellular fractionation demonstrated an association of QM protein with the rough endoplasmic reticulum [1].
• Ribosomal protein L10 interacts with the SH3 domain and regulates GDNF-induced neurite growth in SH-SY-5y cells [2].
• SH-SY-5y human neuroblastoma cells transfected with QM were considerably more susceptible to neurite outgrowth induced by glial cell line-derived neurotrophic factor (GDNF) [2].

Associations of RPL10 with chemical compounds

• Ribosomal protein L10 has 213 amino acids (the NH2-terminal methionine is removed after translation of the mRNA); the molecular weight is 24,456 [13].
• Only one QM was observed from the o-quinone of 4-hydroxyestrone, 4-OHE-QM2 (4-hydroxy-1(2),4(5),9(10)- oestratrien-3,17-dione) which is analogous to the C ring analog (2-OHE-QM2) from the o-quinone of 2-hydroxyestrone [8].
• The o-quinone of 2-hydroxyestrone isomerized to two QMs; a QM stabilized by one alkyl substituent in the B ring, 2-OHE-QM1 (3-hydroxy-1-(10),3(4),5(6)-oestratrien-2,17-dione) and one having two alkyl substituents on the methylene group in the C ring, 2-OHE-QM2 (2-hydroxy-1(2),4(5),9(10)-oestratrien-3,17-dione) [8].
• The effect on Adr resistance of buthionine sulfoximine (BSO, GSH synthesis inhibitor), was studied alone or in combination with verapamil (drug-efflux inhibitor), docosahexaenoic acid (membrane lipid domain affector), ethacrynic acid (GST inhibitor), aphidicolin (DNA-polymerase-alpha inhibitor) or novobiocin (NOV, topo-II inhibitor) [14].
• In contrast, isomerization of the o-quinones to electrophilic quinone methides (4-methylene-2,5-cyclohexadien-1-one, QM) could cause cellular damage primarily through alkylation [10].

Other interactions of RPL10

• We show here with an exon-specific polymerase chain reaction that the genomic homolog of the QM cDNA is located in the G6PD-color vision genes region in Xq28 [15].
• This region and the 5' -half of the transcribed region of the QM gene are enriched for C and G nucleotides with no bias against CpG dinucleotides--indicative of a CpG island [16].
• The QM gene encodes a 24 kDa basic protein that peripherally associates with the ribosomes [17].
• In the amino-terminal region A0 contains an arginine-rich segment which shows a low but distinct similarity to that of bacterial ribosomal protein L10 through which L10 is thought to bind to 23S rRNA [18].

Analytical, diagnostic and therapeutic context of RPL10

• Molecular cloning and expression of a pearl oyster (Pinctada fucata) homologue of mammalian putative tumor suppressor QM [19].
• Southern blot analysis revealed multiple copies of QM within the trypanosome genome [20].
• Serum alpha-1 acid glycoprotein concentration was determined by nephelometry on QM 300 protein analyzer [21].
• Furthermore, we expressed the QM protein in Escherichia coli; Western blotting showed that the antibody of human QM is immunoreactive to the expressed oyster QM protein [19].
• Pharmacokinetic considerations and tests with cell lines and individual cell suspensions from metastatic human solid tumor biopsies suggested testing the efficacy of mitoxantrone (NOV) in intraperitoneal regional chemotherapy (IPRC) [22].

References