RRM2B

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Ribonucleotide reductase M2 B (TP53 inducible)
Protein RRM2B PDB 2VUX.png
Rendering based on PDB 2VUX.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols RRM2B ; MTDPS8A; MTDPS8B; P53R2
External IDs OMIM604712 MGI2155865 HomoloGene56723 ChEMBL: 1896 GeneCards: RRM2B Gene
EC number 1.17.4.1
RNA expression pattern
PBB GE RRM2B gnf1h06036 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 50484 382985
Ensembl ENSG00000048392 ENSMUSG00000022292
UniProt Q7LG56 Q6PEE3
RefSeq (mRNA) NM_001172477 NM_199476
RefSeq (protein) NP_001165948 NP_955770
Location (UCSC) Chr 8:
103.22 – 103.25 Mb
Chr 15:
37.92 – 37.96 Mb
PubMed search [1] [2]

Ribonucleoside-diphosphate reductase subunit M2 B is an enzyme that in humans is encoded by the RRM2B gene.[1][2][3][4] The gene encoding the RRM2B protein is located on chromosome 8, at position 8q23.1. The gene and its products are also known by designations MTDPS8A, MTDPS8B, and p53R2.

Interactions[edit]

RRM2B has been shown to interact with Mdm2[5] and Ataxia telangiectasia mutated.[5]

Clinical relevance[edit]

Mutations in this gene have been shown to cause progressive external ophthalmoplegia.[6] Increased expression of RRM2B has been correlated with gemcitabine resistance in human cholangiocarcinoma cells[7] and may be predictive of lack of clinical benefit from gemcitabine for human cancers.

References[edit]

  1. ^ Tanaka H, Arakawa H, Yamaguchi T, Shiraishi K, Fukuda S, Matsui K, Takei Y, Nakamura Y (Apr 2000). "A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage". Nature 404 (6773): 42–9. doi:10.1038/35003506. PMID 10716435. 
  2. ^ Nakano K, Balint E, Ashcroft M, Vousden KH (Oct 2000). "A ribonucleotide reductase gene is a transcriptional target of p53 and p73". Oncogene 19 (37): 4283–9. doi:10.1038/sj.onc.1203774. PMID 10980602. 
  3. ^ Bourdon A, Minai L, Serre V, Jais JP, Sarzi E, Aubert S, Chretien D, de Lonlay P, Paquis-Flucklinger V, Arakawa H, Nakamura Y, Munnich A, Rotig A (May 2007). "Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion". Nat Genet 39 (6): 776–80. doi:10.1038/ng2040. PMID 17486094. 
  4. ^ "Entrez Gene: RRM2B ribonucleotide reductase M2 B (TP53 inducible)". 
  5. ^ a b Chang L, Zhou B, Hu S, Guo R, Liu X, Jones SN, Yen Y (November 2008). "ATM-mediated serine 72 phosphorylation stabilizes ribonucleotide reductase small subunit p53R2 protein against MDM2 to DNA damage". Proc. Natl. Acad. Sci. U.S.A. 105 (47): 18519–24. doi:10.1073/pnas.0803313105. PMC 2587585. PMID 19015526. 
  6. ^ Takata A, Kato M, Nakamura M, Yoshikawa T, Kanba S, Sano A, Kato T (September 2011). "Exome sequencing identifies a novel missense variant in RRM2B associated with autosomal recessive progressive external ophthalmoplegia". Genome Biol. 12 (9): R92. doi:10.1186/gb-2011-12-9-r92. PMID 21951382. 
  7. ^ Sato J, Kimura T, Saito T, Anazawa T, Kenjo A, Sato Y, Tsuchiya T, Gotoh M (September 2011). "Gene expression analysis for predicting gemcitabine resistance in human cholangiocarcinoma". J Hepatobiliary Pancreat Sci 18 (5): 700–11. doi:10.1007/s00534-011-0376-7. PMID 21451941. 

Further reading[edit]

  • Guittet O, Håkansson P, Voevodskaya N, et al. (2001). "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. 276 (44): 40647–51. doi:10.1074/jbc.M106088200. PMID 11517226. 
  • Yamaguchi T, Matsuda K, Sagiya Y, et al. (2001). "p53R2-dependent pathway for DNA synthesis in a p53-regulated cell cycle checkpoint". Cancer Res. 61 (22): 8256–62. PMID 11719458. 
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. 
  • Yanamoto S, Kawasaki G, Yoshitomi I, Mizuno A (2003). "Expression of p53R2, newly p53 target in oral normal epithelium, epithelial dysplasia and squamous cell carcinoma". Cancer Lett. 190 (2): 233–43. doi:10.1016/S0304-3835(02)00588-8. PMID 12565178. 
  • Xue L, Zhou B, Liu X, et al. (2003). "Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits". Cancer Res. 63 (5): 980–6. PMID 12615712. 
  • Zhou B, Liu X, Mo X, et al. (2003). "The human ribonucleotide reductase subunit hRRM2 complements p53R2 in response to UV-induced DNA repair in cells with mutant p53". Cancer Res. 63 (20): 6583–94. PMID 14583450. 
  • Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. 
  • Shao J, Zhou B, Zhu L, et al. (2004). "In vitro characterization of enzymatic properties and inhibition of the p53R2 subunit of human ribonucleotide reductase". Cancer Res. 64 (1): 1–6. doi:10.1158/0008-5472.CAN-03-3048. PMID 14729598. 
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. 
  • Ceballos E, Muñoz-Alonso MJ, Berwanger B, et al. (2005). "Inhibitory effect of c-Myc on p53-induced apoptosis in leukemia cells. Microarray analysis reveals defective induction of p53 target genes and upregulation of chaperone genes". Oncogene 24 (28): 4559–71. doi:10.1038/sj.onc.1208652. PMID 15856024. 
  • Deng ZL, Xie DW, Bostick RM, et al. (2005). "Novel genetic variations of the p53R2 gene in patients with colorectal adenoma and controls". World J. Gastroenterol. 11 (33): 5169–73. PMID 16127747. 
  • Ohno K, Tanaka-Azuma Y, Yoneda Y, Yamada T (2006). "Genotoxicity test system based on p53R2 gene expression in human cells: examination with 80 chemicals". Mutat. Res. 588 (1): 47–57. doi:10.1016/j.mrgentox.2005.09.002. PMID 16236544. 
  • Qiu W, Zhou B, Darwish D, et al. (2006). "Characterization of enzymatic properties of human ribonucleotide reductase holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits". Biochem. Biophys. Res. Commun. 340 (2): 428–34. doi:10.1016/j.bbrc.2005.12.019. PMID 16376858. 
  • Okumura H, Natsugoe S, Yokomakura N, et al. (2006). "Expression of p53R2 is related to prognosis in patients with esophageal squamous cell carcinoma". Clin. Cancer Res. 12 (12): 3740–5. doi:10.1158/1078-0432.CCR-05-2416. PMID 16778101. 
  • Yen Y, Chu B, Yen C, et al. (2007). "Enzymatic property analysis of p53R2 subunit of human ribonucleotide reductase". Adv. Enzyme Regul. 46: 235–47. doi:10.1016/j.advenzreg.2006.01.016. PMID 16846634. 
  • Lembo D, Donalisio M, Cornaglia M, et al. (2007). "Effect of high-risk human papillomavirus oncoproteins on p53R2 gene expression after DNA damage". Virus Res. 122 (1–2): 189–93. doi:10.1016/j.virusres.2006.06.011. PMID 16872707. 
  • Yokomakura N, Natsugoe S, Okumura H, et al. (2007). "Improvement in radiosensitivity using small interfering RNA targeting p53R2 in esophageal squamous cell carcinoma". Oncol. Rep. 18 (3): 561–7. PMID 17671702.