Project title: Elucidate the role of the MEN1 gene in carcinoid tumors and determine a functional connection between the genes MEN1, Rbp2 and p27

Matthew Meyerson, MD, PhD Dana-Farber Cancer Institute

Matthew Meyerson, MD, PhD
  • Status: Completed
  • Year(s): 2006
  • Research Type: Basic
  • Primary Tumor Site: Small intestine
  • Area of Inquiry: Mapping NET dependencies

General Description

The most common known mutation in human neuroendocrine tumors is in the MEN1 gene. Dr. Meyerson’s laboratory has uncovered a biochemical function for the menin protein produced by this gene. Menin modifies the structure of histone proteins that are bound to DNA. The goal of this project is to map the specific modifications made to the histone proteins and also to look for enzymes whose action counteracts the activity of menin. Since menin function is absent in carcinoid tumors, inhibiting enzymes with opposite activity may be useful for carcinoid treatment.  Researchers hope to elucidate the role of the MEN1 gene in carcinoid tumors and to determine a functional connection between the genes MEN1, Rbp2 and p27.

Results

Meyerson found that MEN1 helps to add an important protein modification (called histone methylation) that controls gene expression, and that MEN1 mutations impair this addition. Based on this discovery, Meyerson hypothesized that it might be possible to partly offset the effects of MEN1 mutations by inhibiting another gene, called RBP2, which removes this same protein modification. In other words, inhibiting RBP2 might help restore the appropriate balance. Remarkably, he found that this approach works: mice carrying mutations in both MEN1 and RBP2 survive much longer than mice carrying only MEN1 mutations.

In July 2011, published results suggest a novel strategy for treating neuroendocrine tumors without menin function (as well as other cancer types) by inhibiting a specific class of enzymes, histone H3 trimethyl-lysine 4 demethylase enzymes. Dr. William Kaelin, a colleague of Dr. Meyerson, identified the first histone H3 trimethyl-lysine 4 demethylase; RBP2. Dr. Meyerson’s team has shown that Rbp2 inhibition can slow tumorigenesis caused by loss of menin function in mice with neuroendocrine tumors. This work suggests that RBP2 inhibitors should be developed and might have anti-cancer effects in patients with neuroendocrine cancers. 

Publications

Francis J, Lin W, Rozenblatt-Rosen O, Meyerson M. The menin tumor suppressor protein is phosphorylated in response to DNA damage. PLoS One. 2011 Jan 14;6(1):e16119. doi: 10.1371/journal.pone.0016119.

1: Agarwal SK. The future: genetics advances in MEN1 therapeutic approaches and management strategies. Endocr Relat Cancer. 2017 Oct;24(10):T119-T134. doi: 10.1530/ERC-17-0199. Review. PubMed PMID: 28899949; PubMed Central PMCID: PMC5679100.

2: Feng Z, Ma J, Hua X. Epigenetic regulation by the menin pathway. Endocr Relat Cancer. 2017 Oct;24(10):T147-T159. doi: 10.1530/ERC-17-0298. Epub 2017 Aug 15. Review. PubMed PMID: 28811300; PubMed Central PMCID: PMC5612327.

3: Yuan Z, Sánchez Claros C, Suzuki M, Maggi EC, Kaner JD, Kinstlinger N, Gorecka J, Quinn TJ, Geha R, Corn A, Pastoriza J, Jing Q, Adem A, Wu H, Alemu G, Du YC, Zheng D, Greally JM, Libutti SK. Loss of MEN1 activates DNMT1 implicating DNA hypermethylation as a driver of MEN1 tumorigenesis. Oncotarget. 2016 Mar 15;7(11):12633-50. doi: 10.18632/oncotarget.7279. PubMed PMID: 26871472; PubMed Central PMCID: PMC4914310.

4: Agarwal SK. Exploring the tumors of multiple endocrine neoplasia type 1 in mouse models for basic and preclinical studies. Int J Endocr Oncol. 2014;1(2):153-161. PubMed PMID: 25685317; PubMed Central PMCID: PMC4327775.

5: Cierpicki T, Grembecka J. Challenges and opportunities in targeting the menin-MLL interaction. Future Med Chem. 2014 Mar;6(4):447-62. doi: 10.4155/fmc.13.214. Review. PubMed PMID: 24635524; PubMed Central PMCID: PMC4138051.

6: Chang CW, Chen CR, Huang CY, Shu WY, Chiang CS, Hong JH, Hsu IC. Comparative transcriptome profiling of an SV40-transformed human fibroblast (MRC5CVI) and its untransformed counterpart (MRC-5) in response to UVB irradiation. PLoS One. 2013 Sep 3;8(9):e73311. doi: 10.1371/journal.pone.0073311. eCollection 2013. PubMed PMID: 24019915; PubMed Central PMCID: PMC3760899.

7: Matkar S, Thiel A, Hua X. Menin: a scaffold protein that controls gene expression and cell signaling. Trends Biochem Sci. 2013 Aug;38(8):394-402. doi: 10.1016/j.tibs.2013.05.005. Epub 2013 Jul 10. Review. PubMed PMID: 23850066; PubMed Central PMCID: PMC3741089.

8: Agarwal SK. Multiple endocrine neoplasia type 1. Front Horm Res. 2013;41:1-15. doi: 10.1159/000345666. Epub 2013 Mar 19. Review. PubMed PMID: 23652667; PubMed Central PMCID: PMC6281166.

9: Fang M, Xia F, Mahalingam M, Virbasius CM, Wajapeyee N, Green MR. MEN1 is a melanoma tumor suppressor that preserves genomic integrity by stimulating transcription of genes that promote homologous recombination-directed DNA repair. Mol Cell Biol. 2013 Jul;33(13):2635-47. doi: 10.1128/MCB.00167-13. Epub 2013 May 6. PubMed PMID: 23648481; PubMed Central PMCID: PMC3700119.

10: Yang YJ, Song TY, Park J, Lee J, Lim J, Jang H, Kim YN, Yang JH, Song Y, Choi A, Lee HY, Jo CH, Han JW, Kim ST, Youn HD, Cho EJ. Menin mediates epigenetic regulation via histone H3 lysine 9 methylation. Cell Death Dis. 2013 Apr 11;4:e583. doi: 10.1038/cddis.2013.98. PubMed PMID: 23579270; PubMed Central PMCID: PMC3668625.

11: Feng ZJ, Gurung B, Jin GH, Yang XL, Hua XX. SUMO modification of menin. Am J Cancer Res. 2013;3(1):96-106. Epub 2013 Jan 18. PubMed PMID: 23359867; PubMed Central PMCID: PMC3555195.

12: Ren F, Xu HW, Hu Y, Yan SH, Wang F, Su BW, Zhao Q. Expression and subcellular localization of menin in human cancer cells. Exp Ther Med. 2012 Jun;3(6):1087-1091. Epub 2012 Mar 29. PubMed PMID: 22970022; PubMed Central PMCID: PMC3438647.

Lin W, Cao J, Liu J, Beshiri ML, Fujiwara Y, Francis J, Cherniack AD, Geisen C, Blair LP, Zou MR, Shen X, Kawamori D, Liu Z, Grisanzio C, Watanabe H, Minamishima YA, Zhang Q, Kulkarni RN, Signoretti S, Rodig SJ, Bronson RT, Orkin SH, Tuck DP, Benevolenskaya, EV, Meyerson M, Kaelin WG, Yan Q. Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1. Proceedings of the National Academy of Sciences Aug 2011, 108 (33) 13379-13386; DOI:10.1073/pnas.1110104108.

  1. Hu D, Jablonowski C, Cheng PH, AlTahan A, Li C, Wang Y, Palmer L, Lan C, Sun B, Abu-Zaid A, Fan Y, Brimble M, Gamboa NT, Kumbhar RC, Yanishevski D, Miller KM, Kang G, Zambetti GP, Chen T, Yan Q, Davidoff AM, Yang J. KDM5A Regulates a
    Translational Program that Controls p53 Protein Expression. iScience. 2018 Nov 30;9:84-100. doi: 10.1016/j.isci.2018.10.012. Epub 2018 Oct 17.
  2. Sun Y, Zhou B, Mao F, Xu J, Miao H, Zou Z, Phuc Khoa LT, Jang Y, Cai S, Witkin M, Koche R, Ge K, Dressler GR, Levine RL, Armstrong SA, Dou Y, Hess JL. HOXA9 Reprograms the Enhancer Landscape to Promote Leukemogenesis. Cancer Cell. 2018 Oct 8;34(4):643-658.e5. doi: 10.1016/j.ccell.2018.08.018. Epub 2018 Sep 27.
  3. Wu L, Cao J, Cai WL, Lang SM, Horton JR, Jansen DJ, Liu ZZ, Chen JF, Zhang M, Mott BT, Pohida K, Rai G, Kales SC, Henderson MJ, Hu X, Jadhav A, Maloney DJ, Simeonov A, Zhu S, Iwasaki A, Hall MD, Cheng X, et al. KDM5 histone demethylases repress immune response via suppression of STING. PLoS Biol. 2018 Aug 6;16(8):e2006134. doi: 10.1371/journal.pbio.2006134. eCollection 2018 Aug.
  4. Schultz LE, Haltom JA, Almeida MP, Wierson WA, Solin SL, Weiss TJ, Helmer JA, Sandquist EJ, Shive HR, McGrail M. Epigenetic regulators Rbbp4 and Hdac1 are overexpressed in a zebrafish model of RB1 embryonal brain tumor, and are required for neural progenitor survival and proliferation. Dis Model Mech. 2018 Jun 15;11(6). pii: dmm034124. doi: 10.1242/dmm.034124.
  5. Drelon C, Belalcazar HM, Secombe J. The Histone Demethylase KDM5 Is Essential for Larval Growth in Drosophila. Genetics. 2018 Jul;209(3):773-787. doi: 10.1534/genetics.118.301004. Epub 2018 May 15.
  6. Iyer S, Agarwal SK. Epigenetic regulation in the tumorigenesis of MEN1-associated endocrine cell types. J Mol Endocrinol. 2018 Jul;61(1):R13-R24. doi: 10.1530/JME-18-0050. Epub 2018 Apr 3. Review.
  7. McBrayer SK, Olenchock BA, DiNatale GJ, Shi DD, Khanal J, Jennings RB, Novak JS, Oser MG, Robbins AK, Modiste R, Bonal D, Moslehi J, Bronson RT, Neuberg D, Nguyen QD, Signoretti S, Losman JA, Kaelin WG Jr. Autochthonous tumors driven by Rb1 loss have an ongoing requirement for the RBP2 histone demethylase. Proc Natl Acad Sci U S A. 2018 Apr 17;115(16):E3741-E3748. doi: 10.1073/pnas.1716029115. Epub 2018 Apr 2.
  8. Horton JR, Liu X, Wu L, Zhang K, Shanks J, Zhang X, Rai G, Mott BT, Jansen DJ, Kales SC, Henderson MJ, Pohida K, Fang Y, Hu X, Jadhav A, Maloney DJ, Hall MD, Simeonov A, Fu H, Vertino PM, Yan Q, Cheng X. Insights into the Action of Inhibitor Enantiomers against Histone Lysine Demethylase 5A. J Med Chem. 2018 Apr 12;61(7):3193-3208. doi: 10.1021/acs.jmedchem.8b00261. Epub 2018 Mar 23.
  9. Harmeyer KM, Facompre ND, Herlyn M, Basu D. JARID1 Histone Demethylases: Emerging Targets in Cancer. Trends Cancer. 2017 Oct;3(10):713-725. doi: 10.1016/j.trecan.2017.08.004. Epub 2017 Sep 12. Review.
  10. Agarwal SK. The future: genetics advances in MEN1 therapeutic approaches and management strategies. Endocr Relat Cancer. 2017 Oct;24(10):T119-T134. doi: 10.1530/ERC-17-0199. Review.
  11. Dreijerink KMA, Timmers HTM, Brown M. Twenty years of menin: emerging opportunities for restoration of transcriptional regulation in MEN1. Endocr Relat Cancer. 2017 Oct;24(10):T135-T145. doi: 10.1530/ERC-17-0281. Epub 2017 Aug 15. Review.
  12. Scahill CM, Digby Z, Sealy IM, Wojciechowska S, White RJ, Collins JE, Stemple DL, Bartke T, Mathers ME, Patton EE, Busch-Nentwich EM. Loss of the chromatin modifier Kdm2aa causes BrafV600E-independent spontaneous melanoma in zebrafish. PLoS Genet. 2017 Aug 14;13(8):e1006959. doi: 10.1371/journal.pgen.1006959. eCollection 2017 Aug.
  13. Balch C, Ramapuram JB, Tiwari AK. The Epigenomics of Embryonic Pathway Signaling in Colorectal Cancer. Front Pharmacol. 2017 May 19;8:267. doi: 10.3389/fphar.2017.00267. eCollection 2017. Review.
  14. Shen H, Xu W, Lan F. Histone lysine demethylases in mammalian embryonic development. Exp Mol Med. 2017 Apr 28;49(4):e325. doi: 10.1038/emm.2017.57. Review.
  15. Dreijerink KMA, Groner AC, Vos ESM, Font-Tello A, Gu L, Chi D, Reyes J, Cook J, Lim E, Lin CY, de Laat W, Rao PK, Long HW, Brown M. Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer. Cell Rep. 2017 Mar 7;18(10):2359-2372. doi: 10.1016/j.celrep.2017.02.025.
  16. D’Oto A, Tian QW, Davidoff AM, Yang J. Histone demethylases and their roles in cancer epigenetics. J Med Oncol Ther. 2016;1(2):34-40.
  17. Blair LP, Liu Z, Labitigan RL, Wu L, Zheng D, Xia Z, Pearson EL, Nazeer FI, Cao J, Lang SM, Rines RJ, Mackintosh SG, Moore CL, Li W, Tian B, Tackett AJ, Yan Q. KDM5 lysine demethylases are involved in maintenance of 3’UTR length. Sci Adv. 2016 Nov 18;2(11):e1501662. doi: 10.1126/sciadv.1501662. eCollection 2016 Nov.
  18. Brier AB, Loft A, Madsen JGS, Rosengren T, Nielsen R, Schmidt SF, Liu Z, Yan Q, Gronemeyer H, Mandrup S. The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation. Nucleic Acids Res. 2017 Feb 28;45(4):1743-1759. doi: 10.1093/nar/gkw1156.
  19. Lin W, Francis JM, Li H, Gao X, Pedamallu CS, Ernst P, Meyerson M. Kmt2a cooperates with menin to suppress tumorigenesis in mouse pancreatic islets. Cancer Biol Ther. 2016 Dec;17(12):1274-1281. doi: 10.1080/15384047.2016.1250986. Epub 2016 Nov 1.
  20. Gale M, Sayegh J, Cao J, Norcia M, Gareiss P, Hoyer D, Merkel JS, Yan Q. Screen-identified selective inhibitor of lysine demethylase 5A blocks cancer cell growth and drug resistance. Oncotarget. 2016 Jun 28;7(26):39931-39944. doi:10.18632/oncotarget.9539.
  21. Maggi EC, Trillo-Tinoco J, Struckhoff AP, Vijayaraghavan J, Del Valle L, Crabtree JS. Retinoblastoma-binding protein 2 (RBP2) is frequently expressed in neuroendocrine tumors and promotes the neoplastic phenotype. Oncogenesis. 2016 Aug 22;5(8):e257. doi: 10.1038/oncsis.2016.58.
  22. Zhaunova L, Ohkura H, Breuer M. Kdm5/Lid Regulates Chromosome Architecture in Meiotic Prophase I Independently of Its Histone Demethylase Activity. PLoS Genet. 2016 Aug 5;12(8):e1006241. doi: 10.1371/journal.pgen.1006241. eCollection 2016 Aug. PubMed [citation] PMID: 27494704, PMCID: PMC4975413
  23. Horton JR, Liu X, Gale M, Wu L, Shanks JR, Zhang X, Webber PJ, Bell JSK, Kales SC, Mott BT, Rai G, Jansen DJ, Henderson MJ, Urban DJ, Hall MD, Simeonov A, Maloney DJ, Johns MA, Fu H, Jadhav A, Vertino PM, Yan Q, et al. Structural Basis for KDM5A Histone Lysine Demethylase Inhibition by Diverse Compounds. Cell Chem Biol. 2016 Jul 21;23(7):769-781. doi: 10.1016/j.chembiol.2016.06.006. Epub 2016 Jul 14.
  24. Dyson NJ. RB1: a prototype tumor suppressor and an enigma. Genes Dev. 2016 Jul 1;30(13):1492-502. doi: 10.1101/gad.282145.116. Review.
  25. Zhou D, Kannappan V, Chen X, Li J, Leng X, Zhang J, Xuan S. RBP2 induces stem-like cancer cells by promoting EMT and is a prognostic marker for renal cell carcinoma. Exp Mol Med. 2016 Jun 10;48:e238. doi: 10.1038/emm.2016.37.
  26. Kohno S, Kitajima S, Sasaki N, Takahashi C. Retinoblastoma tumor suppressor functions shared by stem cell and cancer cell strategies. World J Stem Cells. 2016 Apr 26;8(4):170-84. doi: 10.4252/wjsc.v8.i4.170. Review.
  27. Horton JR, Engstrom A, Zoeller EL, Liu X, Shanks JR, Zhang X, Johns MA, Vertino PM, Fu H, Cheng X. Characterization of a Linked Jumonji Domain of the KDM5/JARID1 Family of Histone H3 Lysine 4 Demethylases. J Biol Chem. 2016 Feb 5;291(6):2631-46. doi: 10.1074/jbc.M115.698449. Epub 2015 Dec 8.
  28. Váraljai R, Islam AB, Beshiri ML, Rehman J, Lopez-Bigas N, Benevolenskaya EV. Increased mitochondrial function downstream from KDM5A histone demethylase rescues differentiation in pRB-deficient cells. Genes Dev. 2015 Sep 1;29(17):1817-34. doi: 10.1101/gad.264036.115. Epub 2015 Aug 27.
  29. Liu H, Liu L, Holowatyj A, Jiang Y, Yang ZQ. Integrated genomic and functional analyses of histone demethylases identify oncogenic KDM2A isoform in breast cancer. Mol Carcinog. 2016 May;55(5):977-90. doi: 10.1002/mc.22341. Epub 2015 Jul 24.
  30. Agarwal SK. Exploring the tumors of multiple endocrine neoplasia type 1 in mouse models for basic and preclinical studies. Int J Endocr Oncol. 2014;1(2):153-161.
  31. Zhu L, Lu Z, Zhao H. Antitumor mechanisms when pRb and p53 are genetically inactivated. Oncogene. 2015 Aug 27;34(35):4547-57. doi: 10.1038/onc.2014.399. Epub 2014 Dec 8. Review.
  32. Liu X, Greer C, Secombe J. KDM5 interacts with Foxo to modulate cellular levels of oxidative stress. PLoS Genet. 2014 Oct 16;10(10):e1004676. doi: 10.1371/journal.pgen.1004676. eCollection 2014 Oct.
  33. Nishibuchi G, Shibata Y, Hayakawa T, Hayakawa N, Ohtani Y, Sinmyozu K, Tagami H, Nakayama J. Physical and functional interactions between the histone H3K4 demethylase KDM5A and the nucleosome remodeling and deacetylase (NuRD) complex. J Biol Chem. 2014 Oct 17;289(42):28956-70. doi: 10.1074/jbc.M114.573725. Epub 2014 Sep 4.
  34. Liang X, Zeng J, Wang L, Shen L, Li S, Ma L, Ci X, Yu J, Jia M, Sun Y, Liu Z, Liu S, Li W, Yu H, Chen C, Jia J. Histone demethylase RBP2 induced by Helicobactor Pylori CagA participates in the malignant transformation of gastric epithelial cells. Oncotarget. 2014 Jul 30;5(14):5798-807.
  35. Zou MR, Cao J, Liu Z, Huh SJ, Polyak K, Yan Q. Histone demethylase jumonji AT-rich interactive domain 1B (JARID1B) controls mammary gland development by regulating key developmental and lineage specification genes. J Biol Chem. 2014 Jun 20;289(25):17620-33. doi: 10.1074/jbc.M114.570853. Epub 2014 May 6.
  36. Li L, Wang L, Song P, Geng X, Liang X, Zhou M, Wang Y, Chen C, Jia J, Zeng J. Critical role of histone demethylase RBP2 in human gastric cancer angiogenesis. Mol Cancer. 2014 Apr 9;13:81. doi: 10.1186/1476-4598-13-81.
  37. Lu Z, Bauzon F, Fu H, Cui J, Zhao H, Nakayama K, Nakayama KI, Zhu L. Skp2 suppresses apoptosis in Rb1-deficient tumours by limiting E2F1 activity. Nat Commun. 2014 Mar 17;5:3463. doi: 10.1038/ncomms4463.
  38. Cao J, Liu Z, Cheung WK, Zhao M, Chen SY, Chan SW, Booth CJ, Nguyen DX, Yan Q. Histone demethylase RBP2 is critical for breast cancer progression and metastasis. Cell Rep. 2014 Mar 13;6(5):868-77. doi: 10.1016/j.celrep.2014.02.004. Epub 2014 Feb 27.
  39. Lin C, Song W, Bi X, Zhao J, Huang Z, Li Z, Zhou J, Cai J, Zhao H. Recent advances in the ARID family: focusing on roles in human cancer. Onco Targets Ther. 2014 Feb 18;7:315-24. doi: 10.2147/OTT.S57023. eCollection 2014. Review.
  40. Mannironi C, Proietto M, Bufalieri F, Cundari E, Alagia A, Danovska S, Rinaldi T, Famiglini V, Coluccia A, La Regina G, Silvestri R, Negri R. An high-throughput in vivo screening system to select H3K4-specific histone demethylase inhibitors. PLoS One. 2014 Jan 29;9(1):e86002. doi: 10.1371/journal.pone.0086002. eCollection 2014.
  41. Wang S, Wang Y, Wu H, Hu L. RBP2 induces epithelial-mesenchymal transition in non-small cell lung cancer. PLoS One. 2013 Dec 20;8(12):e84735. doi: 10.1371/journal.pone.0084735. eCollection 2013.
  42. Matkar S, Thiel A, Hua X. Menin: a scaffold protein that controls gene expression and cell signaling. Trends Biochem Sci. 2013 Aug;38(8):394-402. doi: 10.1016/j.tibs.2013.05.005. Epub 2013 Jul 10. Review.
  43. Shamma A, Suzuki M, Hayashi N, Kobayashi M, Sasaki N, Nishiuchi T, Doki Y, Okamoto T, Kohno S, Muranaka H, Kitajima S, Yamamoto K, Takahashi C. ATM mediates pRB function to control DNMT1 protein stability and DNA methylation. Mol Cell Biol. 2013 Aug;33(16):3113-24. doi: 10.1128/MCB.01597-12. Epub 2013 Jun 10.
  44. Agarwal SK. Multiple endocrine neoplasia type 1. Front Horm Res. 2013;41:1-15. doi: 10.1159/000345666. Epub 2013 Mar 19. Review.
  45. Sayegh J, Cao J, Zou MR, Morales A, Blair LP, Norcia M, Hoyer D, Tackett AJ, Merkel JS, Yan Q. Identification of small molecule inhibitors of Jumonji AT-rich interactive domain 1B (JARID1B) histone demethylase by a sensitive high throughput screen. J Biol Chem. 2013 Mar 29;288(13):9408-17. doi: 10.1074/jbc.M112.419861. Epub 2013 Feb 13.
  46. Tzatsos A, Paskaleva P, Ferrari F, Deshpande V, Stoykova S, Contino G, Wong KK, Lan F, Trojer P, Park PJ, Bardeesy N. KDM2B promotes pancreatic cancer via Polycomb-dependent and -independent transcriptional programs. J Clin Invest. 2013 Feb;123(2):727-39. doi: 10.1172/JCI64535. Epub 2013 Jan 16.
  47. Beshiri ML, Holmes KB, Richter WF, Hess S, Islam AB, Yan Q, Plante L, Litovchick L, Gévry N, Lopez-Bigas N, Kaelin WG Jr, Benevolenskaya EV. Coordinated repression of cell cycle genes by KDM5A and E2F4 during differentiation. Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18499-504. doi: 10.1073/pnas.1216724109. Epub 2012 Oct 23.
  48. Hou J, Wu J, Dombkowski A, Zhang K, Holowatyj A, Boerner JL, Yang ZQ. Genomic amplification and a role in drug-resistance for the KDM5A histone demethylase in breast cancer. Am J Transl Res. 2012;4(3):247-56. Epub 2012 Jul 22.
  49. Cao J, Yan Q. Histone ubiquitination and deubiquitination in transcription, DNA damage response, and cancer. Front Oncol. 2012 Mar 12;2:26. doi: 10.3389/fonc.2012.00026. eCollection 2012.
  50. Chicas A, Kapoor A, Wang X, Aksoy O, Evertts AG, Zhang MQ, Garcia BA, Bernstein E, Lowe SW. H3K4 demethylation by Jarid1a and Jarid1b contributes to retinoblastoma-mediated gene silencing during cellular senescence. Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):8971-6. doi: 10.1073/pnas.1119836109. Epub 2012 May 21.
  51. Gordon GM, Du W. Conserved RB functions in development and tumor suppression. Protein Cell. 2011 Nov;2(11):864-78. doi: 10.1007/s13238-011-1117-z. Epub 2011 Dec 17. Review.
  52. Kaelin WG Jr. Cancer and altered metabolism: potential importance of hypoxia-inducible factor and 2-oxoglutarate-dependent dioxygenases. Cold Spring Harb Symp Quant Biol. 2011;76:335-45. doi: 10.1101/sqb.2011.76.010975. Epub 2011 Nov 16. Review.
  53. Lin W, Cao J, Liu J, Beshiri ML, Fujiwara Y, Francis J, Cherniack AD, Geisen C, Blair LP, Zou MR, Shen X, Kawamori D, Liu Z, Grisanzio C, Watanabe H, Minamishima YA, Zhang Q, Kulkarni RN, Signoretti S, Rodig SJ, Bronson RT, Orkin SH, et al. Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1. Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13379-86. doi: 10.1073/pnas.1110104108. Epub 2011 Jul 25.

 

Additional Details

  • State: Massachusetts
  • Grant Duration: 2 years
  • Awards: No information

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