RRM2

Summary

Gene Symbol: RRM2
Description: ribonucleotide reductase regulatory subunit M2
Alias: RR2, RR2M, ribonucleoside-diphosphate reductase subunit M2, ribonucleotide reductase M2 polypeptide, ribonucleotide reductase small chain, ribonucleotide reductase small subunit
Species: human
Products:     RRM2

Top Publications

  1. Zhou B, Yen Y. Characterization of the human ribonucleotide reductase M2 subunit gene; genomic structure and promoter analyses. Cytogenet Cell Genet. 2001;95:52-9 pubmed
    ..b>RRM2 plays a role in cell proliferation, tumorgenicity, metastasis and drug resistance...
  2. Zhang Y, Jones T, Martin S, Caplen N, Pommier Y. Implication of checkpoint kinase-dependent up-regulation of ribonucleotide reductase R2 in DNA damage response. J Biol Chem. 2009;284:18085-95 pubmed publisher
    ..Silencing of RRM1 and RRM2, which encode the large and small subunits of the human ribonucleotide reductase complex, respectively, markedly ..
  3. Niida H, Katsuno Y, Sengoku M, Shimada M, Yukawa M, Ikura M, et al. Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase. Genes Dev. 2010;24:333-8 pubmed publisher
    ..Here, we found that ribonucleotide reductase (RNR) subunits RRM1 and RRM2 accumulated very rapidly at damage sites. RRM1 bound physically to Tip60...
  4. Morikawa T, Hino R, Uozaki H, Maeda D, Ushiku T, Shinozaki A, et al. Expression of ribonucleotide reductase M2 subunit in gastric cancer and effects of RRM2 inhibition in vitro. Hum Pathol. 2010;41:1742-8 pubmed publisher
    ..Our data suggest that ribonucleotide reductase M2 subunit overexpression could be associated with the gastric cancer progression and that suppression of its function is a potential therapeutic strategy in gastric cancer. ..
  5. Hsu N, Wu J, Liu X, Yen Y, Chen C, Chou M, et al. Expression status of ribonucleotide reductase small subunits hRRM2/p53R2 as prognostic biomarkers in stage I and II non-small cell lung cancer. Anticancer Res. 2011;31:3475-81 pubmed
    ..Based on our finding, p53R2 expression seems more important than that of hRRM2 in prognosis of early-stage lung cancer. ..
  6. D Angiolella V, Donato V, Forrester F, Jeong Y, Pellacani C, Kudo Y, et al. Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair. Cell. 2012;149:1023-34 pubmed publisher
    ..Using affinity purifications and mass spectrometry, we identified RRM2 (the ribonucleotide reductase family member 2) as an interactor of the F-box protein cyclin F...
  7. Jensen R, Page D, Holt J. Identification of genes expressed in premalignant breast disease by microscopy-directed cloning. Proc Natl Acad Sci U S A. 1994;91:9257-61 pubmed
  8. Duxbury M, Ito H, Zinner M, Ashley S, Whang E. RNA interference targeting the M2 subunit of ribonucleotide reductase enhances pancreatic adenocarcinoma chemosensitivity to gemcitabine. Oncogene. 2004;23:1539-48 pubmed
    ..of ribonucleotide 5'-diphosphates to their 2'-deoxynucleotides, is modulated by levels of its M2 subunit (RRM2)...
  9. Zhang K, Hu S, Wu J, Chen L, Lu J, Wang X, et al. Overexpression of RRM2 decreases thrombspondin-1 and increases VEGF production in human cancer cells in vitro and in vivo: implication of RRM2 in angiogenesis. Mol Cancer. 2009;8:11 pubmed publisher
    In addition to its essential role in ribonucleotide reduction, ribonucleotide reductase (RNR) small subunit, RRM2, has been known to play a critical role in determining tumor malignancy...

More Information

Publications120 found, 100 shown here

  1. Morikawa T, Maeda D, Kume H, Homma Y, Fukayama M. Ribonucleotide reductase M2 subunit is a novel diagnostic marker and a potential therapeutic target in bladder cancer. Histopathology. 2010;57:885-92 pubmed publisher
    To examine the immunohistochemical expression and function of ribonucleotide reductase M2 subunit (RRM2), a gemcitabine-related molecule, in bladder cancer...
  2. Lin Z, Lee Y, Lin F, Belcourt M, Li P, Cory J, et al. Reduced level of ribonucleotide reductase R2 subunits increases dependence on homologous recombination repair of cisplatin-induced DNA damage. Mol Pharmacol. 2011;80:1000-12 pubmed publisher
    ..We propose that HRR becomes important for recovery from cisplatin-DNA lesions when the postexcision process of NER is restrained by reduced levels of the R2 subunit and dATP in p53-deficient cancer cells. ..
  3. Wang L, Lu F, Zhang S, Yao R, Xing X, Wei Z. Overexpression of catalytic subunit M2 in patients with ovarian cancer. Chin Med J (Engl). 2012;125:2151-6 pubmed
    ..Catalytic subunit M2 (RRM2) is the main unit modulating the ribonucleotide reductase enzymatic activity...
  4. Zhou B, Mo X, Liu X, Qiu W, Yen Y. Human ribonucleotide reductase M2 subunit gene amplification and transcriptional regulation in a homogeneous staining chromosome region responsible for the mechanism of drug resistance. Cytogenet Cell Genet. 2001;95:34-42 pubmed
    ..Therefore, we conclude that the drug-resistant phenotype is associated with human RRM2 gene amplification from a homogeneous staining chromosome region and altered transcription regulation...
  5. Xue L, Zhou B, Liu X, Qiu W, Jin Z, Yen Y. Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits. Cancer Res. 2003;63:980-6 pubmed
    ..Therefore, the direct interaction of p53 with p53R2 and hRRM2 and the nuclear accumulation of RR subunits after UV exposure might play a pivotal role in DNA repair. ..
  6. Chabes A, Pfleger C, Kirschner M, Thelander L. Mouse ribonucleotide reductase R2 protein: a new target for anaphase-promoting complex-Cdh1-mediated proteolysis. Proc Natl Acad Sci U S A. 2003;100:3925-9 pubmed
    ..The newly discovered p53-induced p53R2 protein that lacks a KEN box may supply deoxyribonucleotides for DNA repair during G(0)G(1). ..
  7. Duxbury M, Whang E. RRM2 induces NF-kappaB-dependent MMP-9 activation and enhances cellular invasiveness. Biochem Biophys Res Commun. 2007;354:190-6 pubmed
    ..The ribonucleotide reductase M2 subunit (RRM2) is a determinant of malignant cellular behavior in a range of human cancers...
  8. Zhou B, Liu X, Mo X, Xue L, Darwish D, Qiu W, et al. The human ribonucleotide reductase subunit hRRM2 complements p53R2 in response to UV-induced DNA repair in cells with mutant p53. Cancer Res. 2003;63:6583-94 pubmed
    ..To further confirm this hypothesis, we examined the effect of RRM2 inhibitors on cells exposed to UV...
  9. Souglakos J, Boukovinas I, Taron M, Mendez P, Mavroudis D, Tripaki M, et al. Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel/gemcitabine. Br J Cancer. 2008;98:1710-5 pubmed publisher
    Ribonucleotide reductase subunits M1 (RRM1) and M2 (RRM2) are involved in the metabolism of gemcitabine (2',2'-difluorodeoxycytidine), which is used for the treatment of nonsmall cell lung cancer...
  10. Guittet O, Hakansson P, Voevodskaya N, Fridd S, Graslund A, Arakawa H, et al. Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro with the R1 protein, which is expressed both in resting cells in response to DNA damage and in proliferating cells. J Biol Chem. 2001;276:40647-51 pubmed
    ..Taken together, our data indicate that the R1 protein can function as the normal partner of the p53R2 protein and that an R1-p53R2 complex can supply resting cells with deoxyribonucleotides for DNA repair. ..
  11. Huang Y, Liu X, Wang Y, Yeh S, Chen C, Nelson R, et al. The prognostic value of ribonucleotide reductase small subunit M2 in predicting recurrence for prostate cancers. Urol Oncol. 2014;32:51.e9-19 pubmed publisher
    To investigate the prognostic significance of ribonucleotide reductase small subunit M2 (RRM2) in low- and intermediate-risk prostate cancer (PCa)...
  12. Qi W, Xu X, Wang M, Xiangyan L, Wang C, Sun L, et al. Inhibition of Wee1 sensitizes AML cells to ATR inhibitor VE-822-induced DNA damage and apoptosis. Biochem Pharmacol. 2019;: pubmed publisher
    ..VE-822 and AZD1775 decreased the protein levels of ribonucleotide reductase M1 (RRM1) and M2 (RRM2) subunits, key enzymes in the synthesis of deoxyribonucleoside triphosphate, which increased DNA replication stress...
  13. Wang C, Zhang W, Fu M, Yang A, Huang H, Xie J. Establishment of human pancreatic cancer gemcitabine‑resistant cell line with ribonucleotide reductase overexpression. Oncol Rep. 2015;33:383-90 pubmed publisher
    ..resistance protein genes, which decreased; by contrast, 5'-nucleotidase, ribonucleotide reductase (RRM) 1 and RRM2 proteins increased (p<0.05). Therefore, a cell line with acquired GEM resistance was established successfully...
  14. Garzón J, Rodríguez R, Kong Z, Chabes A, Rodríguez Acebes S, Méndez J, et al. Shortage of dNTPs underlies altered replication dynamics and DNA breakage in the absence of the APC/C cofactor Cdh1. Oncogene. 2017;36:5808-5818 pubmed publisher
    ..Moreover, exogenous supply of nucleotide precursors, or ectopic overexpression of RRM2, the regulatory subunit of Ribonucleotide Reductase, restore replication efficiency, indicating that dNTP ..
  15. Saxena S, Somyajit K, Nagaraju G. XRCC2 Regulates Replication Fork Progression during dNTP Alterations. Cell Rep. 2018;25:3273-3282.e6 pubmed publisher
    ..The absence of XRCC2 is associated with increased levels of RRM2, the regulatory subunit of ribonucleotide reductase (RNR), and concomitantly high nucleotide pools, leading to ..
  16. Cho J, Kim S, Park S, Kim H, Song S. Suppression of pancreatic adenocarcinoma upregulated factor (PAUF) increases the sensitivity of pancreatic cancer to gemcitabine and 5FU, and inhibits the formation of pancreatic cancer stem like cells. Oncotarget. 2017;8:76398-76407 pubmed publisher
    ..CFPAC-1 decreased the mRNA expression of multidrug resistant protein 5 (MRP5) and ribonucleotide reductase M2 (RRM2) and were more vulnerable to gemcitabine and 5-FU than negative control (p<0.05)...
  17. Foskolou I, Hammond E. RRM2B: An oxygen-requiring protein with a role in hypoxia. Mol Cell Oncol. 2017;4:e1335272 pubmed publisher
    ..provides cells with deoxyribonucleotides, responds to limited oxygen availability by switching small subunits from RRM2 to RRM2B...
  18. Sahoo A, Lee B, Boniface K, Seneschal J, Sahoo S, Seki T, et al. MicroRNA-211 Regulates Oxidative Phosphorylation and Energy Metabolism in Human Vitiligo. J Invest Dermatol. 2017;137:1965-1974 pubmed publisher
    ..in vitiligo cell line PIG3V and skin biopsy samples from vitiligo patients, whereas its predicted targets PPARGC1A, RRM2, and TAOK1 were reciprocally up-regulated...
  19. Thomas A, Coarfa C, Qian J, Wilkerson J, Rajapakshe K, Krett N, et al. Identification of potential glucocorticoid receptor therapeutic targets in multiple myeloma. Nucl Recept Signal. 2015;13:e006 pubmed publisher
    ..As a proof of principle, we have verified two targets, namely RRM2 and BCL2L1, as primary functional targets of GR involved in GC-induced cell death.
  20. Suzuki M, Kobayashi M, Ohno T, Kanamori S, Tateishi S, Murai A, et al. Genetic dissection of the fatty liver QTL Fl1sa by using congenic mice and identification of candidate genes in the liver and epididymal fat. BMC Genet. 2016;17:145 pubmed
    ..In the liver, mRNA levels of Iah1 (in R2) and Rrm2 (in R2) were significantly different in A/J-12SM mice from those in A/J mice...
  21. Sayou C, Millán Zambrano G, Santos Rosa H, Petfalski E, Robson S, Houseley J, et al. RNA Binding by Histone Methyltransferases Set1 and Set2. Mol Cell Biol. 2017;37: pubmed publisher
    ..Set1 lacking RNA recognition motif 2 (RRM2) showed reduced in vivo cross-linking to RNA and reduced chromatin occupancy...
  22. Wang C, Yu T, Tan L, Cheng J. Bioinformatics analysis of gene expression profile in callus tissues of osteoporotic phenotype mice induced by osteoblast-specific Krm2 overexpression. Int J Rheum Dis. 2016;19:1263-1271 pubmed publisher
    ..Other hub nodes, such as Ccnb2 and Rrm2, were closely associated with the p53 signaling pathway...
  23. Holmes B, Lee J, Landon K, Benavides Serrato A, Bashir T, Jung M, et al. Mechanistic Target of Rapamycin (mTOR) Inhibition Synergizes with Reduced Internal Ribosome Entry Site (IRES)-mediated Translation of Cyclin D1 and c-MYC mRNAs to Treat Glioblastoma. J Biol Chem. 2016;291:14146-59 pubmed publisher
    ..heterogeneous nuclear ribonucleoprotein A1, and docking analysis suggested a small pocket within close proximity to RRM2 as the potential binding site...
  24. Zhou S, Li J, Xu H, Zhang S, Chen X, Chen W, et al. Liposomal curcumin alters chemosensitivity of breast cancer cells to Adriamycin via regulating microRNA expression. Gene. 2017;622:1-12 pubmed publisher
    ..results showed that MAPK, mTOR, PI3K-Akt, AMPK, TNF, Ras signaling pathways and several target genes such as PPARG, RRM2, SRSF1and EPAS1, may associate with drug resistance of breast cancer cells to Adr...
  25. Chen H, Li L, Chen X, Yang M, Ye Y, Wang X, et al. The mechanism of Jurkat cells apoptosis induced by Aggregatibacter actinomycetemcomitans cytolethal distending toxin. Apoptosis. 2017;22:841-851 pubmed publisher
    ..proteins (SMNDC1, TNFRSF10B, UBE2I, ITM2A, CASP3, P53, EIF1, TCF3, HMGN5, CASP8) were up-regulated and 7 proteins (RRM2, TPX2, KIF11, NUCKS1, TOP2A, XRCC1, PTPLAD1, RRM2) were down-regulated, (vi) one possible apoptotic pathway [Ubc9 (..
  26. Martin F, Talikka M, Hoeng J, Peitsch M. Identification of gene expression signature for cigarette smoke exposure response--from man to mouse. Hum Exp Toxicol. 2015;34:1200-11 pubmed publisher
    ..g., lung) is not readily accessible. The signature consisted of LRRN3, SASH1, PALLD, RGL1, TNFRSF17, CDKN1C, IGJ, RRM2, ID3, SERPING1, and FUCA1...
  27. Kosmacz M, Luzarowski M, Kerber O, Leniak E, Gutiérrez Beltrán E, Moreno J, et al. Interaction of 2',3'-cAMP with Rbp47b Plays a Role in Stress Granule Formation. Plant Physiol. 2018;177:411-421 pubmed publisher
    ..in 2',3'-cAMP-treated Arabidopsis seedlings, and interactions between 2',3'-cAMP and RNA-binding domains of Rbp47b, RRM2 and RRM3, were confirmed in vitro using microscale thermophoresis...
  28. Ganguly A, Verma G, Bhavesh N. The N-terminal RNA Recognition Motif of PfSR1 Confers Semi-specificity for Pyrimidines during RNA Recognition. J Mol Biol. 2019;431:498-510 pubmed publisher
    ..we have also ascertained the purine preference of PfSR1 to be a property of the carboxy terminal pseudo-RRM (RRM2), which binds RNA non-canonically and with greater affinity compared to RRM1...
  29. Kobayashi A, Kanaba T, Satoh R, Ito Y, Sugiura R, Mishima M. Chemical shift assignments of the first and second RRMs of Nrd1, a fission yeast MAPK-target RNA binding protein. Biomol NMR Assign. 2017;11:123-126 pubmed publisher
    ..Here we report the 1H, 13C, and 15N resonance assignments of RRM1-RRM2 (residues 108-284) comprising the first and second RRMs obtained using heteronuclear NMR techniques...
  30. Tang X, Xu Y, Lu L, Jiao Y, Liu J, Wang L, et al. Identification of key candidate genes and small molecule drugs in cervical cancer by bioinformatics strategy. Cancer Manag Res. 2018;10:3533-3549 pubmed publisher
    ..associated with longer overall survival, and the survival was significantly better in the low-expression RRM2 group. Moreover, CMap predicted nine small molecules as possible adjuvant drugs to treat CC...
  31. Steinmeyer N, Doller A, Biyanee A, Brauss T, Schmid T, Pfeilschifter J, et al. Lymphotoxin α, a novel target of posttranscriptional gene regulation by HuR in HepG2 cells. FEBS Lett. 2015;589:1943-50 pubmed publisher
    ..Furthermore, electrophoretic mobility shift assay (EMSA) implicates that the RNA-binding critically depends on the RNA recognition motif 2 (RRM2) and the hinge region of HuR.
  32. Lopez G, Braggio D, Zewdu A, Casadei L, Batte K, Bid H, et al. Mocetinostat combined with gemcitabine for the treatment of leiomyosarcoma: Preclinical correlates. PLoS ONE. 2017;12:e0188859 pubmed publisher
    ..Mocetinostat reduced the expression of gemcitabine-resistance markers RRM1, RRM2, and increased the expression of gemcitabine-sensitivity marker, hENT1, in LMS cells...
  33. Jia M, Gut H, Chao J. Structural basis of IMP3 RRM12 recognition of RNA. RNA. 2018;24:1659-1666 pubmed publisher
    ..The spatial orientation of RRM1 to RRM2 is unique compared with other known tandem RRM structures...
  34. Mujo A, Lixa C, Carneiro L, Anobom C, Almeida F, Pinheiro A. (1)H, (15)N and (13)C resonance assignments of the RRM1 domain of the key post-transcriptional regulator HuR. Biomol NMR Assign. 2015;9:281-4 pubmed publisher
    ..HuR is composed of three functional domains, known as RNA-recognition motifs (RRM1, RRM2 and RRM3). It is known that RRM1 is the most important domain for mRNA-binding affinity...
  35. Zhu K, Chen P, Zhang D, Yan H, Liu H, Cen L, et al. Association of genetic polymorphisms in genes involved in Ara-C and dNTP metabolism pathway with chemosensitivity and prognosis of adult acute myeloid leukemia (AML). J Transl Med. 2018;16:90 pubmed publisher
    ..Trait Loci) single nucleotide polymorphisms (SNPs) or tag SNPs in 7 genes including CMPK1, NME1, NME2, RRM1, RRM2, SAMHD1 and E2F1 were genotyped in 361 Chinese non-M3 AML patients by using the Sequenom Massarray system...
  36. Chen P, Wu J, Shu Y, Jiang H, Zhao X, Qian H, et al. Gemcitabine resistance mediated by ribonucleotide reductase M2 in lung squamous cell carcinoma is reversed by GW8510 through autophagy induction. Clin Sci (Lond). 2018;132:1417-1433 pubmed publisher
    ..Some studies suggest that overexpressions of ribonucleotide reductase (RNR) subunit M2 (RRM2) may be involved in gemcitabine resistance...
  37. Zhao H, Zhang H, Du Y, Gu X. Prognostic significance of BRCA1, ERCC1, RRM1, and RRM2 in patients with advanced non-small cell lung cancer receiving chemotherapy. Tumour Biol. 2014;35:12679-88 pubmed publisher
    ..1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1), and ribonucleotide reductase subunit M2 (RRM2) in patients with advanced non-small cell lung cancer (NSCLC) who received platinum-based chemotherapy...
  38. Liu X, Xu Z, Hou C, Wang M, Chen X, Lin Q, et al. Inhibition of hepatitis B virus replication by targeting ribonucleotide reductase M2 protein. Biochem Pharmacol. 2016;103:118-28 pubmed publisher
    ..By performing computer-assisted virtual screening against the crystal structure of RR small subunit M2 (RRM2), osalmid, was identified as a potential RRM2-targeting compound...
  39. Cáceres C, Contreras N, Angulo J, Vera Otarola J, Pino Ajenjo C, Llorian M, et al. Polypyrimidine tract-binding protein binds to the 5' untranslated region of the mouse mammary tumor virus mRNA and stimulates cap-independent translation initiation. FEBS J. 2016;283:1880-901 pubmed publisher
    ..Mutational analysis reveals that stimulation of MMTV-IRES activity is abrogated when PTB1 is mutated either in RRM1/RRM2 or RRM3/RRM4...
  40. Chen Y, Tsou B, Hu S, Ma H, Liu X, Yen Y, et al. Autophagy induction causes a synthetic lethal sensitization to ribonucleotide reductase inhibition in breast cancer cells. Oncotarget. 2016;7:1984-99 pubmed publisher
    ..Induction of autophagy reduced cellular levels of RRM2, a subunit of ribonucleotide reductase (RR), the rate limiting enzyme in the production of deoxyribonucleotide ..
  41. Taricani L, Shanahan F, Malinao M, Beaumont M, Parry D. A functional approach reveals a genetic and physical interaction between ribonucleotide reductase and CHK1 in mammalian cells. PLoS ONE. 2014;9:e111714 pubmed publisher
    Ribonucleotide reductase (RNR) enzyme is composed of the homodimeric RRM1 and RRM2 subunits, which together form a heterotetramic active enzyme that catalyzes the de novo reduction of ribonucleotides to generate deoxyribonucleotides (..
  42. Zhao X, Wang X, Sun W, Cheng K, Qin H, Han X, et al. Precision design of nanomedicines to restore gemcitabine chemosensitivity for personalized pancreatic ductal adenocarcinoma treatment. Biomaterials. 2018;158:44-55 pubmed publisher
    ..is the major GEM transporter across cell membranes) and increased expression of ribonucleotide reductase subunit 2 (RRM2, which decreases the cytotoxicity of GEM) was associated with low GEM chemosensitivity...
  43. Boukovinas I, Papadaki C, Mendez P, Taron M, Mavroudis D, Koutsopoulos A, et al. Tumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients. PLoS ONE. 2008;3:e3695 pubmed publisher
    Overexpression of RRM1 and RRM2 has been associated with gemcitabine resistance. BRCA1 overexpression increases sensitivity to paclitaxel and docetaxel...
  44. Gong C, Liu H, Song R, Zhong T, Lou M, Wang T, et al. ATR-CHK1-E2F3 signaling transactivates human ribonucleotide reductase small subunit M2 for DNA repair induced by the chemical carcinogen MNNG. Biochim Biophys Acta. 2016;1859:612-26 pubmed publisher
    ..In this study, we demonstrated that the RRM2 gene was transactivated by MNNG exposure more strongly than the other small subunit, p53R2...
  45. Kunicka T, Prochazka P, Krus I, Bendova P, Protivova M, Susova S, et al. Molecular profile of 5-fluorouracil pathway genes in colorectal carcinoma. BMC Cancer. 2016;16:795 pubmed
    ..Downregulation of DPYD and upregulation of PPAT, UMPS, RRM2, and SLC29A1 transcripts were found in tumors compared to adjacent mucosa in testing and validation sets of ..
  46. Brown K, Sharifi S, Hussain R, Donaldson L, Bayfield M, Wilson D. Distinct Dynamic Modes Enable the Engagement of Dissimilar Ligands in a Promiscuous Atypical RNA Recognition Motif. Biochemistry. 2016;55:7141-7150 pubmed publisher
    ..characterize the changes in dynamics that accompany oligonucleotide binding in the atypical RNA recognition motif (RRM2) in the C-terminal domain (CTD) of human La protein...
  47. Martínez Lumbreras S, Taverniti V, Zorrilla S, Séraphin B, Pérez Cañadillas J. Gbp2 interacts with THO/TREX through a novel type of RRM domain. Nucleic Acids Res. 2016;44:437-48 pubmed publisher
    ..Gbp2 RRM1 and RRM2 recognise preferentially RNAs containing the core motif GGUG...
  48. Lu A, Feng H, Wang P, Han D, Chen X, Zheng M. Emerging roles of the ribonucleotide reductase M2 in colorectal cancer and ultraviolet-induced DNA damage repair. World J Gastroenterol. 2012;18:4704-13 pubmed
    To investigate the roles of the ribonucleotide reductase M2 (RRM2) subunit in colorectal cancer (CRC) and ultraviolet (UV)-induced DNA damage repair...
  49. Allouch A, David A, Amie S, Lahouassa H, Chartier L, Margottin Goguet F, et al. p21-mediated RNR2 repression restricts HIV-1 replication in macrophages by inhibiting dNTP biosynthesis pathway. Proc Natl Acad Sci U S A. 2013;110:E3997-4006 pubmed publisher
    ..Our findings unravel a cellular pathway that restricts HIV-1 and other primate lentiviruses by affecting dNTP synthesis, thereby pointing to new potential cellular targets for anti-HIV therapeutic strategies. ..
  50. Fang Z, Song R, Gong C, Zhang X, Ren G, Li J, et al. Ribonucleotide reductase large subunit M1 plays a different role in the invasion and metastasis of papillary thyroid carcinoma and undifferentiated thyroid carcinoma. Tumour Biol. 2016;37:3515-26 pubmed publisher
    ..Here, we first examined the expression level of three RR subunit proteins (RRM1, RRM2, and RRM2B) in papillary thyroid carcinoma (PTC) and undifferentiated thyroid carcinoma (UTC) patient samples by ..
  51. Stankovic N, Schloesser M, Joris M, Sauvage E, Hanikenne M, Motte P. Dynamic Distribution and Interaction of the Arabidopsis SRSF1 Subfamily Splicing Factors. Plant Physiol. 2016;170:1000-13 pubmed publisher
    ..mutagenesis of SR34 RNA-binding sequences and Arg/Ser-rich (RS) domain, we further show that functional RRM1 or RRM2 are dispensable for the exclusive protein nuclear localization and speckle-like distribution...
  52. Grolmusz V, Karaszi K, Micsik T, Toth E, Mészáros K, Karvaly G, et al. Cell cycle dependent RRM2 may serve as proliferation marker and pharmaceutical target in adrenocortical cancer. Am J Cancer Res. 2016;6:2041-2053 pubmed
    ..Upon the comparative reanalysis, ribonucleotide reductase subunit 2 (RRM2), responsible for the ribonucleotide dezoxyribonucleotide conversion during the S phase of the cell cycle has been ..
  53. Beusch I, Barraud P, Moursy A, Cléry A, Allain F. Tandem hnRNP A1 RNA recognition motifs act in concert to repress the splicing of survival motor neuron exon 7. elife. 2017;6: pubmed publisher
    ..b>RRM2 binds to the upstream motif and RRM1 to the downstream motif...
  54. Morgan B, Zitzewitz J, Massi F. Structural Rearrangement upon Fragmentation of the Stability Core of the ALS-Linked Protein TDP-43. Biophys J. 2017;113:540-549 pubmed publisher
    ..Fragmentation within the second RNA recognition motif (RRM2) of TDP-43 has been observed in patient tissues and may play a role in the formation of aggregates in disease...
  55. Wu B, Su S, Patil D, Liu H, Gan J, Jaffrey S, et al. Molecular basis for the specific and multivariant recognitions of RNA substrates by human hnRNP A2/B1. Nat Commun. 2018;9:420 pubmed publisher
    ..A2/B1 in complex with various RNA substrates, elucidating specific recognitions of AGG and UAG motifs by RRM1 and RRM2 domains, respectively...
  56. Yang Feng T, Barton D, Thelander L, Lewis W, Srinivasan P, Francke U. Ribonucleotide reductase M2 subunit sequences mapped to four different chromosomal sites in humans and mice: functional locus identified by its amplification in hydroxyurea-resistant cell lines. Genomics. 1987;1:77-86 pubmed
    ..In the human genome, four chromosomal sites carrying RRM2-related sequences were identified at 1p31----p33, 1q21----q23, 2p24----p25, and Xp11----p21...
  57. Fisher S, Patel S, Bagci P, Kooby D, El Rayes B, Staley C, et al. An analysis of human equilibrative nucleoside transporter-1, ribonucleoside reductase subunit M1, ribonucleoside reductase subunit M2, and excision repair cross-complementing gene-1 expression in patients with resected pancreas adenocarcinoma: implic. Cancer. 2013;119:445-53 pubmed publisher
    ..Human equilibrative nucleoside transporter-1 (hENT1) and ribonucleoside reductase subunits M1 and M2 (RRM1 and RRM2) are integral to cellular transport and DNA synthesis and are implicated as poor prognostic factors in other ..
  58. Sun L, Lü J, Niu Z, Ding K, Bi D, Liu S, et al. A Potent Chemotherapeutic Strategy with Eg5 Inhibitor against Gemcitabine Resistant Bladder Cancer. PLoS ONE. 2015;10:e0144484 pubmed publisher
    ..According to the result of Human OneArray GeneChip, RRM1 and RRM2 were up-regulated, while there was no significant change in Eg5...
  59. Sanokawa Akakura R, Akakura S, Tabibzadeh S. Replicative Senescence in Human Fibroblasts Is Delayed by Hydrogen Sulfide in a NAMPT/SIRT1 Dependent Manner. PLoS ONE. 2016;11:e0164710 pubmed publisher
    ..appear including accumulation of SA-?-Gal, enhanced expression of p16, p21, and RRM2B while the expression of RRM2, hTERT, SIRT1, NAMPT, and NAD/NADH ratio all fall...
  60. Castelblanco E, Zafon C, Maravall J, Gallel P, Martínez M, Capel I, et al. APLP2, RRM2, and PRC1: New Putative Markers for the Differential Diagnosis of Thyroid Follicular Lesions. Thyroid. 2017;27:59-66 pubmed publisher
    ..A model based on the nuclear and cytoplasmic expression of APLP2, RRM2, and PRC1 discriminated between benign and malignant lesions with 100% sensitivity in both main and validation ..
  61. Wei Y, Lim L, Wang L, Song J. ALS-causing cleavages of TDP-43 abolish its RRM2 structure and unlock CTD for enhanced aggregation and toxicity. Biochem Biophys Res Commun. 2017;485:826-831 pubmed publisher
    ..While the ?35-kDa fragments contain entire RRM1, RRM2 and C-terminal domain (CTD) with a middle hydrophobic segment flanked by two prion-like regions; the ?25-kDa one ..
  62. Rejiba S, Bigand C, Parmentier C, Hajri A. Gemcitabine-based chemogene therapy for pancreatic cancer using Ad-dCK::UMK GDEPT and TS/RR siRNA strategies. Neoplasia. 2009;11:637-50 pubmed
    ..monophosphate kinase fusion gene (dCK::UMK) and small interference RNA directed against ribonucleotide reductase (RRM2) and thymidylate synthase (TS)...
  63. Mah V, Alavi M, Márquez Garbán D, Maresh E, Kim S, Horvath S, et al. Ribonucleotide reductase subunit M2 predicts survival in subgroups of patients with non-small cell lung carcinoma: effects of gender and smoking status. PLoS ONE. 2015;10:e0127600 pubmed publisher
    ..The functional enzyme consists of two subunits - one large (RRM1) and one small (RRM2 or RRM2b) subunit...
  64. Marnef A, Jády B, Kiss T. Human polypyrimidine tract-binding protein interacts with mitochondrial tRNA(Thr) in the cytosol. Nucleic Acids Res. 2016;44:1342-53 pubmed publisher
    ..PTB forms a direct interaction with the T-loop and the D-stem-loop of mt tRNA(Thr) using its N-terminal RRM1 and RRM2 motifs...
  65. Kobayashi M, Suzuki M, Ohno T, Tsuzuki K, Taguchi C, Tateishi S, et al. Detection of differentially expressed candidate genes for a fatty liver QTL on mouse chromosome 12. BMC Genet. 2016;17:73 pubmed publisher
    ..The mRNA levels of three genes (Iah1, Rrm2, Prkd1) in the chromosomal region of Fl1sa were significantly different between the strains...
  66. Yan D, Wang W. [SATB1 promotes the malignant of human non-Hodgkin lymphoma by activating the ribonucleotide reductase ?small subunit M2]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2016;41:1155-1162 pubmed
    To explore the role of the special AT rich sequence binding protein-1 (SATB1) and ribonucleotide reductase M2 (RRM2) in enhancing malignant progression of non-Hodgkin lymphoma (NHL)...
  67. Tryfonidis K, Papadaki C, Assele S, Lagoudaki E, Menis J, Koutsopoulos A, et al. Association of BRCA1, ERCC1, RAP80, PKM2, RRM1, RRM2, TS, TSP1, and TXR1 mRNA expression levels between primary tumors and infiltrated regional lymph nodes in patients with resectable non-small cell lung cancer. Pharmacogenomics J. 2019;19:15-24 pubmed publisher
    ..PT and LNs samples)-case and 56 PT only samples-control cohorts] were analyzed for BRCA1, ERCC1, RAP80, PKM2, RRM1, RRM2, TS, TSP1, and TXR1 mRNA expression by quantitative real-time polymerase-chain reaction (PCR)...
  68. Wang Y, Zhi Q, Ye Q, Zhou C, Zhang L, Yan W, et al. SCYL1-BP1 affects cell cycle arrest in human hepatocellular carcinoma cells via Cyclin F and RRM2. Anticancer Agents Med Chem. 2016;16:440-6 pubmed
    ..Furthermore, SCYL1-BP1 sustained RRM2 protein expression by reducing its ubiquitination...
  69. Kolwicz S, Odom G, Nowakowski S, Moussavi Harami F, Chen X, Reinecke H, et al. AAV6-mediated Cardiac-specific Overexpression of Ribonucleotide Reductase Enhances Myocardial Contractility. Mol Ther. 2016;24:240-250 pubmed publisher
    ..and promotor portions of the human cardiac troponin T gene (TNNT2) ligated to rat cDNAs encoding either the Rrm1 or Rrm2 subunit...
  70. Rasmussen R, Gajjar M, Tučková L, Jensen K, Maya Mendoza A, Holst C, et al. BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity. Nat Commun. 2016;7:13398 pubmed publisher
    ..Mechanistically, we identify a novel role of BRCA1 as a transcriptional co-activator of RRM2 (catalytic subunit of ribonucleotide reductase), whereby BRCA1-mediated RRM2 expression protects GBM cells from ..
  71. Iradi M, Triplett J, Thomas J, Davila R, Crown A, Brown H, et al. Characterization of gene regulation and protein interaction networks for Matrin 3 encoding mutations linked to amyotrophic lateral sclerosis and myopathy. Sci Rep. 2018;8:4049 pubmed publisher
    ..Remarkably, deletion of the RRM2 motif caused enhanced binding of >100 hundred proteins...
  72. Pavloff N, Rivard D, Masson S, Shen S, Mes Masson A. Sequence analysis of the large and small subunits of human ribonucleotide reductase. DNA Seq. 1992;2:227-34 pubmed
    ..3% homology downstream of amino acid 68 of the human and mouse R2 proteins. However, the amino-terminal portions of these two proteins are more divergent in sequence, with only 69.2% homology in the first 68 amino acids. ..
  73. Lin Z, Belcourt M, Cory J, Sartorelli A. Stable suppression of the R2 subunit of ribonucleotide reductase by R2-targeted short interference RNA sensitizes p53(-/-) HCT-116 colon cancer cells to DNA-damaging agents and ribonucleotide reductase inhibitors. J Biol Chem. 2004;279:27030-8 pubmed
    ..The findings provide evidence that R2-RNR can be employed to supply dNTPs for the repair of DNA damage in cells with an impaired p53-dependent induction of p53R2. ..
  74. Qiu W, Zhou B, Darwish D, Shao J, Yen Y. Characterization of enzymatic properties of human ribonucleotide reductase holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits. Biochem Biophys Res Commun. 2006;340:428-34 pubmed
    ..Taken together, the eukaryotic expression system RR holoenzyme will provide a very useful tool to understand the molecular mechanisms of RR activity and the interactions of its subunits. ..
  75. Attia S, Kolesar J, Mahoney M, Pitot H, Laheru D, Heun J, et al. A phase 2 consortium (P2C) trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) for advanced adenocarcinoma of the pancreas. Invest New Drugs. 2008;26:369-79 pubmed publisher
    ..In conclusion, this regimen appears inactive against predominantly GR pancreatic cancer. RR M2 protein may not have a critical role in the malignant potential of pancreatic cancer. ..
  76. Mannava S, Moparthy K, Wheeler L, Leonova K, Wawrzyniak J, Bianchi Smiraglia A, et al. Ribonucleotide reductase and thymidylate synthase or exogenous deoxyribonucleosides reduce DNA damage and senescence caused by C-MYC depletion. Aging (Albany NY). 2012;4:917-22 pubmed
    ..Our data demonstrate the essential role of TS and RR in C-MYC-dependent suppression of senescence in melanoma cells. ..
  77. Coskunpinar E, Yildiz P, Aynaci E, Turna A, Musteri Oltulu Y, Hekimoglu E, et al. Investigation of some DNA repair genes association in non small cell lung cancer. Cell Mol Biol (Noisy-le-grand). 2015;61:57-62 pubmed
    Ribonucleoside-diphosphate reductase subunit M2, also known as ribonucleotide reductase small subunit, is an enzyme that in humans is encoded by the RRM2 gene and also Ribonucleoside-diphosphate reductase large subunit is an enzyme that ..
  78. Anacker D, Aloor H, Shepard C, Lenzi G, Johnson B, Kim B, et al. HPV31 utilizes the ATR-Chk1 pathway to maintain elevated RRM2 levels and a replication-competent environment in differentiating Keratinocytes. Virology. 2016;499:383-396 pubmed publisher
    ..Here, we demonstrate that HPV31 positive cells exhibit increased dNTP pools and levels of RRM2, a component of the ribonucleotide reductase (RNR) complex, which is required for de novo synthesis of dNTPs...
  79. He Z, Hu X, Liu W, Dorrance A, Garzon R, Houghton P, et al. P53 suppresses ribonucleotide reductase via inhibiting mTORC1. Oncotarget. 2017;8:41422-41431 pubmed publisher
    ..We report here that p53 suppresses ribonucleotide reductase subunit 1 (RRM1) and 2 (RRM2) via inhibiting mammalian target of rapamycin complex 1 (mTORC1)...
  80. Kashlan O, Scott C, Lear J, Cooperman B. A comprehensive model for the allosteric regulation of mammalian ribonucleotide reductase. Functional consequences of ATP- and dATP-induced oligomerization of the large subunit. Biochemistry. 2002;41:462-74 pubmed
    ..The similar specific activities of R1(2)R2(2) and R1(6)R2(6) are inconsistent with a proposed model for R2(2) docking with R1(2) [Uhlin, U., and Eklund, H. (1994) Nature 370, 533-539], and an alternative is suggested. ..
  81. Xiao G, Zhou B, Somlo G, Portnow J, Juhasz A, Un F, et al. Identification of F-box/LLR-repeated protein 17 as potential useful biomarker for breast cancer therapy. Cancer Genomics Proteomics. 2008;5:151-60 pubmed
    ..Further characterization revealed that FBXL17 [corrected] directly interacts with the human RR M2 (RRM2) subunit to promote hRRM2 overexpression in the breast cancer cell line MCF-7...
  82. Aye Y, Stubbe J. Clofarabine 5'-di and -triphosphates inhibit human ribonucleotide reductase by altering the quaternary structure of its large subunit. Proc Natl Acad Sci U S A. 2011;108:9815-20 pubmed publisher
    ..This is the first example of hexamerization of ? induced by an NDP analog that reversibly binds at the active site. ..
  83. Ricardo Lax I, Ramanan V, Michailidis E, Shamia T, Reuven N, Rice C, et al. Hepatitis B virus induces RNR-R2 expression via DNA damage response activation. J Hepatol. 2015;63:789-96 pubmed publisher
    ..This suggests that inhibition of this pathway may have a therapeutic value for HBV carriers. ..
  84. Fang Z, Lin A, Chen J, Zhang X, Liu H, Li H, et al. CREB1 directly activates the transcription of ribonucleotide reductase small subunit M2 and promotes the aggressiveness of human colorectal cancer. Oncotarget. 2016;7:78055-78068 pubmed publisher
    As the small subunit of Ribonucleotide reductase (RR), RRM2 displays a very important role in various critical cellular processes such as cell proliferation, DNA repair, and senescence, etc...
  85. Potts K, Irwin C, Favis N, Pink D, Vincent K, Lewis J, et al. Deletion of F4L (ribonucleotide reductase) in vaccinia virus produces a selective oncolytic virus and promotes anti-tumor immunity with superior safety in bladder cancer models. EMBO Mol Med. 2017;9:638-654 pubmed publisher
    ..gene that encodes the virus homolog of the cell-cycle-regulated small subunit of ribonucleotide reductase (RRM2)...
  86. Shetty S, Marudamuthu A, Abernathy D, Shetty R, Shetty P, Fu J, et al. Regulation of urokinase expression at the posttranscription level by lung epithelial cells. Biochemistry. 2012;51:205-13 pubmed publisher
    ..We purified the uPA mRNA 3'UTR binding protein and identified it as ribonucleotide reductase M2 (RRM2). We expressed recombinant RRM2 and confirmed its interaction with a specific 66 nt uPA 3'UTR sequence...
  87. Xie H, Lin J, Thomas D, Jiang W, Liu X. Ribonucleotide reductase M2 does not predict survival in patients with resectable pancreatic adenocarcinoma. Int J Clin Exp Pathol. 2012;5:347-55 pubmed
    Ribonucleotide reductase M2 (RRM2) was associated with pancreatic tumor progression and resistance to gemcitabine...
  88. Zhang M, Wang J, Yao R, Wang L. Small interfering RNA (siRNA)-mediated silencing of the M2 subunit of ribonucleotide reductase: a novel therapeutic strategy in ovarian cancer. Int J Gynecol Cancer. 2013;23:659-66 pubmed publisher
    ..the effects of small interfering RNA (siRNA)-mediated silencing of the ribonucleotide reductase M2 subunit (RRM2) on the apoptosis and the drug sensitivity of cisplatin-resistant SKOV3/DDP cells...
  89. Chan A, Persad S, Litchfield D, Wright J. Ribonucleotide reductase R2 protein is phosphorylated at serine-20 by P34cdc2 kinase. Biochim Biophys Acta. 1999;1448:363-71 pubmed
    ..Comparison of ribonucleotide reductase activities between wild type and mutated forms of the R2 proteins suggested that mutation at serine-20 did not significantly affect enzyme activity. ..
  90. Huynh N, Ma C, Giang N, Hagopian J, Ngo J, Adams J, et al. Allosteric interactions direct binding and phosphorylation of ASF/SF2 by SRPK1. Biochemistry. 2009;48:11432-40 pubmed publisher
    ASF/SF2, a member of the serine-arginine (SR) protein family, has two RRM domains (RRM1 and RRM2) and a C-terminal domain rich in RS dipeptides...
  91. Yoshida Y, Tsunoda T, Doi K, Tanaka Y, Fujimoto T, Machida T, et al. KRAS-mediated up-regulation of RRM2 expression is essential for the proliferation of colorectal cancer cell lines. Anticancer Res. 2011;31:2535-9 pubmed
    ..Of these genes, we focused on ribonucleotide reductase M2 (RRM2), which was reported to be associated with DNA synthesis...
  92. Zhang H, Liu X, Warden C, Huang Y, Loera S, Xue L, et al. Prognostic and therapeutic significance of ribonucleotide reductase small subunit M2 in estrogen-negative breast cancers. BMC Cancer. 2014;14:664 pubmed publisher
    Ribonucleotide reductase (RR) is an essential enzyme involved in DNA synthesis. We hypothesized that RR subunit M2 (RRM2) might be a novel prognostic and predictive biomarker for estrogen receptor (ER)-negative breast cancers...