Mutt, SJ, Karhu, T., Lehtonen, S., Lehenkari, P., Carlberg, C., Saarnio, J., Et

Total Page:16

File Type:pdf, Size:1020Kb

Mutt, SJ, Karhu, T., Lehtonen, S., Lehenkari, P., Carlberg, C., Saarnio, J., Et Larriba et al. Vitamin D and signaling pathways Mutt, S. J., Karhu, T., Lehtonen, S., Lehenkari, P., Carlberg, C., Saarnio, J., Seoane, S., and Pérez-Fernández, R. (2006). The vitamin D receptor represses tran- et al. (2012). Inhibition of cytokine secretion from adipocytes by 1,25- scription of the pituitary transcription factor Pit-1 gene without involvement dihydroxyvitamin D3 via the NF-κBpathway.FASEB J. 26, 4400–4407. doi: of the retinoid X receptor. Mol. Endocrinol. 20, 735–748. doi: 10.1210/me.2005- 10.1096/fj.12-210880 0253 Ng, K. Y., Ma, M. T., Leung, K. K., and Leung, P. S. (2010). Vitamin D and vita- Sertznig, P., Dunlop, T., Seifert, M., Tilgen, W., and Reichrath, J. (2009a). min A receptor expression and the proliferative effects of ligand activation of Cross-talk between vitamin D receptor (VDR)- and peroxisome proliferator- these receptors on the development of pancreatic progenitor cells derived from activated receptor (PPAR)-signaling in melanoma cells. Anticancer Res. 29, human fetal pancreas. Stem Cell Rev. 7, 53–63. doi: 10.1007/s12015-010-9146-1 3647–3658. Oh, Y. S., Kim, E. J., Schaffer, B. S., Kang, Y. H., Binderup, L., MacDonald, R. G., Sertznig, P., Seifert, M., Tilgen, W., and Reichrath, J. (2009b). Activation of et al. (2001). Synthetic low-calcaemic vitamin D3 analogues inhibit secretion of vitamin D receptor (VDR)- and peroxisome proliferator-activated receptor insulin-like growth factor II and stimulate production of insulin-like growth (PPAR)-signaling pathways through 1,25(OH)2D3 in melanoma cell lines factor-binding protein-6 in conjunction with growth suppression of HT-29 and other skin-derived cell lines. Dermatoendocrinology 1, 232–238. doi: colon cancer cells. Mol. Cell. Endocrinol. 183, 141–149. doi: 10.1016/S0303- 10.4161/derm.1.4.9629 7207(01)00598-6 Shah, S., Islam, M. N., Dakshanamurthy, S., Rizvi, I., Rao, M., Herrell, R., et al. Okuda, N., Takeda, S., Shinomiya, K., Muneta, T., Itoh, S., Noda, M., et al. (2007). (2006). The molecular basis of vitamin D receptor and β-catenin crossregula- ED-71, a novel vitamin D analog, promotes bone formation and angiogenesis tion. Mol. Cell 21, 799–809. doi: 10.1016/j.molcel.2006.01.037 and inhibits bone resorption after bone marrow ablation. Bone 40, 281–292. doi: Shalhoub, V., Shatzen, E. M., Ward, S. C., Young, J. I., Boedigheimer, M., Twehues, 10.1016/j.bone.2006.08.017 L., et al. (2010). Chondro/osteoblastic and cardiovascular gene modulation in Pálmer, H. G., González-Sancho, J. M., Espada, J., Berciano, M. T., Puig, I., Baulida, human artery smooth muscle cells that calcify in the presence of phosphate and J., et al. (2001). Vitamin D3 promotes the differentiation of colon carcinoma calcitriol or paricalcitol. J. Cell. Biochem. 111, 911–921. doi: 10.1002/jcb.22779 cells by the induction of E-cadherin and the inhibition of β-catenin signaling. Shen, Q., and Christakos, S. (2005). The vitamin D receptor, Runx2, and the Notch J. Cell Biol. 154, 369–387. doi: 10.1083/jcb.200102028 signaling pathway cooperate in the transcriptional regulation of osteopontin. Pálmer, H. G., Sánchez-Carbayo, M., Ordóñez-Morán, P., Larriba, M. J., Cordón- J. Biol. Chem. 280, 40589–40598. doi: 10.1074/jbc.M504166200 Cardó, C., and Muñoz, A. (2003). Genetic signatures of differentiation induced Shen, X., Mula, R. V. R., Li, J., Weigel, N. L., and Falzon, M. (2007). PTHrP by 1α,25-dihydroxyvitamin D3 in human colon cancer cells. Cancer Res. 63, contributes to the anti-proliferative and integrin α6β4-regulating effects of 1,25- 7799–7806. dihydroxyvitamin D3. Steroids 72, 930–938. doi: 10.1016/j.steroids.2007.08.003 Pan, Q., and Simpson, R. U. (1999). c-Myc intron element-binding proteins are Staal,A.,Birkenhäger,J.C.,Pols,H.A.P.,Buurman,C.J.,Vink-vanWijngaarden, required for 1,25-dihydroxyvitamin D3 regulation of c-myc during HL-60 cell T., Kleinekoort, W. M., et al. (1994). Transforming growth factor β-induced differentiation and the involvement of HOXB4. J. Biol. Chem. 274, 8437–8444. dissociation between vitamin D receptor level and 1,25-dihydroxyvitamin D3 doi: 10.1074/jbc.274.13.8437 action in osteoblast-like cells. Bone Miner. 26, 27–42. doi: 10.1016/S0169- Parikh, G., Varadinova, M., Suwandhi, P., Araki, T., Rosenwaks, Z., Poretsky, L., 6009(08)80160-2 et al. (2010). Vitamin D regulates steroidogenesis and insulin-like growth factor Staal, A., Geertsma-Kleinekoort, W. M. C., Van Den Bemd, G. J. C. M., Buurman, binding protein-1 (IGFBP-1) production in human ovarian cells. Horm. Metab. C. J., Birkenhäger, J. C., Pols, H. A. P., et al. (1998). Regulation of osteocal- Res. 42, 754–757. doi: 10.1055/s-0030-1262837 cin production and bone resorption by 1,25-dihydroxyvitamin D3 in mouse Pickup, M., Novitskiy, S., and Moses, H. L. (2013). The roles of TGFβ in the tumour long bones: interaction with the bone-derived growth factors TGF-β and IGF-I. microenvironment. Nat. Rev. Cancer 13, 788–799. doi: 10.1038/nrc3500 J. Bone Miner. Res. 13, 36–43. doi: 10.1359/jbmr.1998.13.1.36 Qadan, L. R., Perez-Stable, C. M., Schwall, R. H., Burnstein, K. L., Ostenson, R. C., Staal, A., Van Wijnen, A. J., Desai, R. K., Pols, H. A. P., Birkenhäger, J. C., Howard, G. A., et al. (2000). Hepatocyte growth factor and vitamin D cooper- Deluca, H. F., et al. (1996). Antagonistic effects of transforming growth atively inhibit androgen-unresponsive prostate cancer cell lines. Endocrinology factor-β on vitamin D3 enhancement of osteocalcin and osteopontin tran- 141, 2567–2573. doi: 10.1210/endo.141.7.7546 scription: reduced interactions of vitamin D receptor/retinoid X receptor com- Reichrath, S., and Reichrath, J. (2012). No evidence for induction of key com- plexes with vitamin E response elements. Endocrinology 137, 2001–2011. doi: ponents of the Notch signaling pathway (Notch-1, Jagged-1) by treatment 10.1210/endo.137.5.8612541 with UV-B, 1,25(OH)2D3, and/or epigenetic drugs (TSA, 5-Aza) in human Stambolsky, P., Tabach, Y., Fontemaggi, G., Weisz, L., Maor-Aloni, R., Siegfried, keratinocytes in vitro. Dermatoendocrinology 4, 44–52. doi: 10.4161/derm. Z., et al. (2010). Modulation of the vitamin D3 response by cancer-associated 19027 mutant p53. Cancer Cell 17, 273–285. doi: 10.1016/j.ccr.2009.11.025 Ren, Z., Li, W., Zhao, Q., Ma, L., and Zhu, J. (2012). The impact of 1,25- Sun, J., Kong, J., Duan, Y., Szeto, F. L., Liao, A., Madara, J. L., et al. (2006). Increased dihydroxyvitamin D3 on the expressions of vascular endothelial growth factor NF-κB activity in fibroblasts lacking the vitamin D receptor. Am. J. Physiol. and transforming growth factor-β1 in the retinas of rats with diabetes. Diabetes Endocrinol. Metab. 291, E315–E322. doi: 10.1152/ajpendo.00590.2005 Res. Clin. Pract. 98, 474–480. doi: 10.1016/j.diabres.2012.09.028 Swami, S., Krishnan, A. V., Peng, L., Lundqvist, J., and Feldman, D. (2013). Rodilla, V., Villanueva, A., Obrador-Hevia, A., Robert-Moreno, A., Fernandez- Transrepression of the estrogen receptor promoter by calcitriol in human breast Majada, V., Grilli, A., et al. (2009). Jagged1 is the pathological link between cancer cells via two negative vitamin D response elements. Endocr. Relat. Cancer Wnt and Notch pathways in colorectal cancer. Proc. Natl. Acad. Sci. U.S.A. 106, 20, 565–577. doi: 10.1530/ERC-12-0281 6315–6320. doi: 10.1073/pnas.0813221106 Tang, J. Y., Xiao, T. Z., Oda, Y., Chang, K. S., Shpall, E., Wu, A., et al. (2011). Vitamin Ryynänen, J., and Carlberg, C. (2013). Primary 1,25-dihydroxyvitamin D3 response D3 inhibits hedgehog signaling and proliferation in murine basal cell carcino- of the interleukin 8 gene cluster in human monocyte- and macrophage-like cells. mas. Cancer Prev. Res. 4, 744–751. doi: 10.1158/1940-6207.CAPR-10-0285 PLoS ONE 8:e78170. doi: 10.1371/journal.pone.0078170 Tang, W. B., Ling, G. H., Sun, L., and Liu, F. Y. (2010). Smad anchor for recep- Salehi-Tabar, R., Nguyen-Yamamoto, L., Tavera-Mendoza, L. E., Quail, T., tor activation (SARA) in TGF-β signaling. Front. Biosci. 2, 857–860. doi: Dimitrov, V., An, B. S., et al. (2012). Vitamin D receptor as a master regulator 10.2741/E147 of the c-MYC/MXD1 network. Proc. Natl. Acad. Sci. U.S.A. 109, 18827–18832. Tavera-Mendoza, L., Wang, T. T., Lallemant, B., Zhang, R., Nagai, Y., Bourdeau, doi: 10.1073/pnas.1210037109 V., et al. (2006). Convergence of vitamin D and retinoic acid signalling Schauber, J., Dorschner, R. A., Coda, A. B., Buchau, A. S., Liu, P. T., Kiken, D., et al. at a common hormone response element. EMBO Rep. 7, 180–185. doi: (2007). Injury enhances TLR2 function and antimicrobial peptide expression 10.1038/sj.embor.7400594 through a vitamin D-dependent mechanism. J. Clin. Invest. 117, 803–811. doi: Thorne, J. L., Maguire, O., Doig, C. L., Battaglia, S., Fehr, L., Sucheston, L. E., et al. 10.1172/JCI30142 (2011). Epigenetic control of a VDR-governed feed-forward loop that regulates Schlaeppi, J. M., Gutzwiller, S., Finkenzeller, G., and Fournier, B. (1997). 1,25- p21waf1/cip1 expression and function in non-malignant prostate cells. Nucleic Dihydroxyvitamin D3 induces the expression of vascular endothelial growth Acids Res. 39, 2045–2056. doi: 10.1093/nar/gkq875 factor in osteoblastic cells. Endocr. Res. 23, 213–229. Ting, H. J., Bao, B. Y., Hsu, C. L., and Lee, Y. F. (2005). Androgen-receptor coregu- Schnabel, M., Fichtel, I., Gotzen, L., and Schlegel, J.
Recommended publications
  • Synergistic Interplay Between PHF8 and HER2 Signaling Contributes to Breast Cancer Development and Drug Resistance
    bioRxiv preprint doi: https://doi.org/10.1101/682476; this version posted June 25, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Synergistic interplay between PHF8 and HER2 signaling contributes to breast cancer development and drug resistance Qi Liu1, Nicholas Borcherding2, Peng Shao1,3, Peterson Kariuki Maina1,4, Weizhou Zhang5, and Hank Heng Qi1,6 1 Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA, 2 Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA, 3 Current address: Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA, 4 Current Address: Albert Einstein College of Medicine, Bronx, NY 10461, USA 5 Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, 32610-0275, USA 6 To whom correspondence should be addressed. Tel: 1-319-335-3084; Fax: 1-319-335-7198; Email: [email protected] Key words: PHF8, HER2, IL-6, breast cancer, drug resistance 1 bioRxiv preprint doi: https://doi.org/10.1101/682476; this version posted June 25, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract HER2 plays a critical role in tumorigenesis and is associated with poor prognosis of HER2- positive breast cancers. Although, anti-HER2 drugs show benefits in breast cancer therapy, de novo or acquired resistance often develop.
    [Show full text]
  • KDM5B Promotes Drug Resistance by Regulating Melanoma-Propagating Cell Subpopulations Xiaoni Liu1,2, Shang-Min Zhang1, Meaghan K
    Published OnlineFirst December 6, 2018; DOI: 10.1158/1535-7163.MCT-18-0395 Cancer Biology and Translational Studies Molecular Cancer Therapeutics KDM5B Promotes Drug Resistance by Regulating Melanoma-Propagating Cell Subpopulations Xiaoni Liu1,2, Shang-Min Zhang1, Meaghan K. McGeary1,2, Irina Krykbaeva1,2, Ling Lai3, Daniel J. Jansen4, Stephen C. Kales4, Anton Simeonov4, Matthew D. Hall4, Daniel P. Kelly3, Marcus W. Bosenberg1,2,5, and Qin Yan1 Abstract Tumor heterogeneity is a major challenge for cancer elevated KDM5B expression, melanoma cells shift toward a À treatment, especially due to the presence of various sub- more drug-tolerant, CD34 state upon exposure to BRAF populations with stem cell or progenitor cell properties. inhibitor or combined BRAF inhibitor and MEK inhibitor þ À þ In mouse melanomas, both CD34 p75 (CD34 )and treatment. KDM5B loss or inhibition shifts melanoma cells À À À þ CD34 p75 (CD34 ) tumor subpopulations were charac- to the more BRAF inhibitor–sensitive CD34 state. These terized as melanoma-propagating cells (MPC) that exhibit results support that KDM5B is a critical epigenetic regulator some of those key features. However, these two subpopula- that governs the transition of key MPC subpopulations tions differ from each other in tumorigenic potential, with distinct drug sensitivity. This study also emphasizes ability to recapitulate heterogeneity, and chemoresistance. the importance of continuing to advance our understand- þ À In this study, we demonstrate that CD34 and CD34 ing of intratumor heterogeneity and ultimately develop V600E subpopulations carrying the BRAF mutation confer novel therapeutics by altering the heterogeneous character- differential sensitivity to targeted BRAF inhibition.
    [Show full text]
  • Small Molecule Inhibitors of KDM5 Histone Demethylases Increase the Radiosensitivity of Breast Cancer Cells Overexpressing JARID1B
    molecules Article Small Molecule Inhibitors of KDM5 Histone Demethylases Increase the Radiosensitivity of Breast Cancer Cells Overexpressing JARID1B Simone Pippa 1, Cecilia Mannironi 2, Valerio Licursi 1,3, Luca Bombardi 1, Gianni Colotti 2, Enrico Cundari 2, Adriano Mollica 4, Antonio Coluccia 5 , Valentina Naccarato 5, Giuseppe La Regina 5 , Romano Silvestri 5 and Rodolfo Negri 1,2,* 1 Department of Biology and Biotechnology “C. Darwin”, Sapienza University of Rome, 00185 Rome, Italy; [email protected] (S.P.); [email protected] (V.L.); [email protected] (L.B.) 2 Institute of Molecular Biology and Pathology, Italian National Research Council, 00185 Rome, Italy; [email protected] (C.M.); [email protected] (G.C.); [email protected] (E.C.) 3 Institute for Systems Analysis and Computer Science “A. Ruberti”, Italian National Research Council, 00185 Rome, Italy 4 Department of Pharmacy, University “G. d’ Annunzio” of Chieti, Via dei Vestini 31, 66100 Chieti, Italy; [email protected] 5 Department of Drug Chemistry and Technologies, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia Cenci Bolognetti Foundation, Sapienza University of Rome, 00185 Rome, Italy; [email protected] (A.C.); [email protected] (V.N.); [email protected] (G.L.R.); [email protected] (R.S.) * Correspondence: [email protected]; Tel.: +39-06-4991-7790 Academic Editors: Sergio Valente and Diego Muñoz-Torrero Received: 12 October 2018; Accepted: 1 May 2019; Published: 4 May 2019 Abstract: Background: KDM5 enzymes are H3K4 specific histone demethylases involved in transcriptional regulation and DNA repair. These proteins are overexpressed in different kinds of cancer, including breast, prostate and bladder carcinomas, with positive effects on cancer proliferation and chemoresistance.
    [Show full text]
  • Table S1 the Four Gene Sets Derived from Gene Expression Profiles of Escs and Differentiated Cells
    Table S1 The four gene sets derived from gene expression profiles of ESCs and differentiated cells Uniform High Uniform Low ES Up ES Down EntrezID GeneSymbol EntrezID GeneSymbol EntrezID GeneSymbol EntrezID GeneSymbol 269261 Rpl12 11354 Abpa 68239 Krt42 15132 Hbb-bh1 67891 Rpl4 11537 Cfd 26380 Esrrb 15126 Hba-x 55949 Eef1b2 11698 Ambn 73703 Dppa2 15111 Hand2 18148 Npm1 11730 Ang3 67374 Jam2 65255 Asb4 67427 Rps20 11731 Ang2 22702 Zfp42 17292 Mesp1 15481 Hspa8 11807 Apoa2 58865 Tdh 19737 Rgs5 100041686 LOC100041686 11814 Apoc3 26388 Ifi202b 225518 Prdm6 11983 Atpif1 11945 Atp4b 11614 Nr0b1 20378 Frzb 19241 Tmsb4x 12007 Azgp1 76815 Calcoco2 12767 Cxcr4 20116 Rps8 12044 Bcl2a1a 219132 D14Ertd668e 103889 Hoxb2 20103 Rps5 12047 Bcl2a1d 381411 Gm1967 17701 Msx1 14694 Gnb2l1 12049 Bcl2l10 20899 Stra8 23796 Aplnr 19941 Rpl26 12096 Bglap1 78625 1700061G19Rik 12627 Cfc1 12070 Ngfrap1 12097 Bglap2 21816 Tgm1 12622 Cer1 19989 Rpl7 12267 C3ar1 67405 Nts 21385 Tbx2 19896 Rpl10a 12279 C9 435337 EG435337 56720 Tdo2 20044 Rps14 12391 Cav3 545913 Zscan4d 16869 Lhx1 19175 Psmb6 12409 Cbr2 244448 Triml1 22253 Unc5c 22627 Ywhae 12477 Ctla4 69134 2200001I15Rik 14174 Fgf3 19951 Rpl32 12523 Cd84 66065 Hsd17b14 16542 Kdr 66152 1110020P15Rik 12524 Cd86 81879 Tcfcp2l1 15122 Hba-a1 66489 Rpl35 12640 Cga 17907 Mylpf 15414 Hoxb6 15519 Hsp90aa1 12642 Ch25h 26424 Nr5a2 210530 Leprel1 66483 Rpl36al 12655 Chi3l3 83560 Tex14 12338 Capn6 27370 Rps26 12796 Camp 17450 Morc1 20671 Sox17 66576 Uqcrh 12869 Cox8b 79455 Pdcl2 20613 Snai1 22154 Tubb5 12959 Cryba4 231821 Centa1 17897
    [Show full text]
  • Modes of Interaction of KMT2 Histone H3 Lysine 4 Methyltransferase/COMPASS Complexes with Chromatin
    cells Review Modes of Interaction of KMT2 Histone H3 Lysine 4 Methyltransferase/COMPASS Complexes with Chromatin Agnieszka Bochy ´nska,Juliane Lüscher-Firzlaff and Bernhard Lüscher * ID Institute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, Pauwelsstrasse 30, 52057 Aachen, Germany; [email protected] (A.B.); jluescher-fi[email protected] (J.L.-F.) * Correspondence: [email protected]; Tel.: +49-241-8088850; Fax: +49-241-8082427 Received: 18 January 2018; Accepted: 27 February 2018; Published: 2 March 2018 Abstract: Regulation of gene expression is achieved by sequence-specific transcriptional regulators, which convey the information that is contained in the sequence of DNA into RNA polymerase activity. This is achieved by the recruitment of transcriptional co-factors. One of the consequences of co-factor recruitment is the control of specific properties of nucleosomes, the basic units of chromatin, and their protein components, the core histones. The main principles are to regulate the position and the characteristics of nucleosomes. The latter includes modulating the composition of core histones and their variants that are integrated into nucleosomes, and the post-translational modification of these histones referred to as histone marks. One of these marks is the methylation of lysine 4 of the core histone H3 (H3K4). While mono-methylation of H3K4 (H3K4me1) is located preferentially at active enhancers, tri-methylation (H3K4me3) is a mark found at open and potentially active promoters. Thus, H3K4 methylation is typically associated with gene transcription. The class 2 lysine methyltransferases (KMTs) are the main enzymes that methylate H3K4. KMT2 enzymes function in complexes that contain a necessary core complex composed of WDR5, RBBP5, ASH2L, and DPY30, the so-called WRAD complex.
    [Show full text]
  • Imidazopyridines As Potent KDM5 Demethylase Inhibitors Promoting Reprogramming Efficiency of Human Ipscs
    Article Imidazopyridines as Potent KDM5 Demethylase Inhibitors Promoting Reprogramming Efficiency of Human iPSCs Yasamin Dabiri, Rodrigo A. Gama- Brambila, Katerina Taskova, ..., Jichang Wang, Miguel A. Andrade-Navarro, Xinlai Cheng [email protected] HIGHLIGHTS O4I3 supports the maintenance and generation of human iPSCs O4I3 is a potent H3K4 demethylase KDM5 inhibitor in vitro and in cells KDM5A, but not KDM5B, serves as an epigenetic barrier of reprogramming Chemical or genetic inhibition of KDM5A tends to promote the reprogramming efficiency Dabiri et al., iScience 12,168– 181 February 22, 2019 ª 2019 The Author(s). https://doi.org/10.1016/ j.isci.2019.01.012 Article Imidazopyridines as Potent KDM5 Demethylase Inhibitors Promoting Reprogramming Efficiency of Human iPSCs Yasamin Dabiri,1 Rodrigo A. Gama-Brambila,1 Katerina Taskova,2,3 Kristina Herold,4 Stefanie Reuter,4 James Adjaye,5 Jochen Utikal,6 Ralf Mrowka,4 Jichang Wang,7 Miguel A. Andrade-Navarro,2,3 and Xinlai Cheng1,8,* SUMMARY Pioneering human induced pluripotent stem cell (iPSC)-based pre-clinical studies have raised safety concerns and pinpointed the need for safer and more efficient approaches to generate and maintain patient-specific iPSCs. One approach is searching for compounds that influence pluripotent stem cell reprogramming using functional screens of known drugs. Our high-throughput screening of drug-like hits showed that imidazopyridines—analogs of zolpidem, a sedative-hypnotic drug—are able to improve reprogramming efficiency and facilitate reprogramming of resistant human primary fibro- blasts. The lead compound (O4I3) showed a remarkable OCT4 induction, which at least in part is 1Institute of Pharmacy and due to the inhibition of H3K4 demethylase (KDM5, also known as JARID1).
    [Show full text]
  • The Roles of Histone Deacetylase 5 and the Histone Methyltransferase Adaptor WDR5 in Myc Oncogenesis
    The Roles of Histone Deacetylase 5 and the Histone Methyltransferase Adaptor WDR5 in Myc oncogenesis By Yuting Sun This thesis is submitted in fulfilment of the requirements for the degree of Doctor of Philosophy at the University of New South Wales Children’s Cancer Institute Australia for Medical Research School of Women’s and Children’s Health, Faculty of Medicine University of New South Wales Australia August 2014 PLEASE TYPE THE UNIVERSITY OF NEW SOUTH WALES Thesis/Dissertation Sheet Surname or Family name: Sun First name: Yuting Other name/s: Abbreviation for degree as given in the University calendar: PhD School : School of·Women's and Children's Health Faculty: Faculty of Medicine Title: The Roles of Histone Deacetylase 5 and the Histone Methyltransferase Adaptor WDR5 in Myc oncogenesis. Abstract 350 words maximum: (PLEASE TYPE) N-Myc Induces neuroblastoma by regulating the expression of target genes and proteins, and N-Myc protein is degraded by Fbxw7 and NEDD4 and stabilized by Aurora A. The class lla histone deacetylase HDAC5 suppresses gene transcription, and blocks myoblast and leukaemia cell differentiation. While histone H3 lysine 4 (H3K4) trimethylation at target gene promoters is a pre-requisite for Myc· induced transcriptional activation, WDRS, as a histone H3K4 methyltransferase presenter, is required for H3K4 methylation and transcriptional activation mediated by a histone H3K4 methyltransferase complex. Here, I investigated the roles of HDAC5 and WDR5 in N-Myc overexpressing neuroblastoma. I have found that N-Myc upregulates HDAC5 protein expression, and that HDAC5 represses NEDD4 gene expression, increases Aurora A gene expression and consequently upregulates N-Myc protein expression in neuroblastoma cells.
    [Show full text]
  • RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases
    G C A T T A C G G C A T genes Review RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases Amber Willbanks, Shaun Wood and Jason X. Cheng * Department of Pathology, Hematopathology Section, University of Chicago, Chicago, IL 60637, USA; [email protected] (A.W.); [email protected] (S.W.) * Correspondence: [email protected] Abstract: Chromatin structure plays an essential role in eukaryotic gene expression and cell identity. Traditionally, DNA and histone modifications have been the focus of chromatin regulation; however, recent molecular and imaging studies have revealed an intimate connection between RNA epigenetics and chromatin structure. Accumulating evidence suggests that RNA serves as the interplay between chromatin and the transcription and splicing machineries within the cell. Additionally, epigenetic modifications of nascent RNAs fine-tune these interactions to regulate gene expression at the co- and post-transcriptional levels in normal cell development and human diseases. This review will provide an overview of recent advances in the emerging field of RNA epigenetics, specifically the role of RNA modifications and RNA modifying proteins in chromatin remodeling, transcription activation and RNA processing, as well as translational implications in human diseases. Keywords: 5’ cap (5’ cap); 7-methylguanosine (m7G); R-loops; N6-methyladenosine (m6A); RNA editing; A-to-I; C-to-U; 2’-O-methylation (Nm); 5-methylcytosine (m5C); NOL1/NOP2/sun domain Citation: Willbanks, A.; Wood, S.; (NSUN); MYC Cheng, J.X. RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases. Genes 2021, 12, 627.
    [Show full text]
  • Protein Identities in Evs Isolated from U87-MG GBM Cells As Determined by NG LC-MS/MS
    Protein identities in EVs isolated from U87-MG GBM cells as determined by NG LC-MS/MS. No. Accession Description Σ Coverage Σ# Proteins Σ# Unique Peptides Σ# Peptides Σ# PSMs # AAs MW [kDa] calc. pI 1 A8MS94 Putative golgin subfamily A member 2-like protein 5 OS=Homo sapiens PE=5 SV=2 - [GG2L5_HUMAN] 100 1 1 7 88 110 12,03704523 5,681152344 2 P60660 Myosin light polypeptide 6 OS=Homo sapiens GN=MYL6 PE=1 SV=2 - [MYL6_HUMAN] 100 3 5 17 173 151 16,91913397 4,652832031 3 Q6ZYL4 General transcription factor IIH subunit 5 OS=Homo sapiens GN=GTF2H5 PE=1 SV=1 - [TF2H5_HUMAN] 98,59 1 1 4 13 71 8,048185945 4,652832031 4 P60709 Actin, cytoplasmic 1 OS=Homo sapiens GN=ACTB PE=1 SV=1 - [ACTB_HUMAN] 97,6 5 5 35 917 375 41,70973209 5,478027344 5 P13489 Ribonuclease inhibitor OS=Homo sapiens GN=RNH1 PE=1 SV=2 - [RINI_HUMAN] 96,75 1 12 37 173 461 49,94108966 4,817871094 6 P09382 Galectin-1 OS=Homo sapiens GN=LGALS1 PE=1 SV=2 - [LEG1_HUMAN] 96,3 1 7 14 283 135 14,70620005 5,503417969 7 P60174 Triosephosphate isomerase OS=Homo sapiens GN=TPI1 PE=1 SV=3 - [TPIS_HUMAN] 95,1 3 16 25 375 286 30,77169764 5,922363281 8 P04406 Glyceraldehyde-3-phosphate dehydrogenase OS=Homo sapiens GN=GAPDH PE=1 SV=3 - [G3P_HUMAN] 94,63 2 13 31 509 335 36,03039959 8,455566406 9 Q15185 Prostaglandin E synthase 3 OS=Homo sapiens GN=PTGES3 PE=1 SV=1 - [TEBP_HUMAN] 93,13 1 5 12 74 160 18,68541938 4,538574219 10 P09417 Dihydropteridine reductase OS=Homo sapiens GN=QDPR PE=1 SV=2 - [DHPR_HUMAN] 93,03 1 1 17 69 244 25,77302971 7,371582031 11 P01911 HLA class II histocompatibility antigen,
    [Show full text]
  • Mutations in PHF8 Are Associated with X Linked Mental Retardation And
    780 J Med Genet: first published as 10.1136/jmg.2004.029439 on 30 September 2005. Downloaded from LETTER TO JMG Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate F Laumonnier*, S Holbert*, N Ronce, F Faravelli, S Lenzner, C E Schwartz, J Lespinasse, H Van Esch, D Lacombe, C Goizet, F Phan-Dinh Tuy, H van Bokhoven, J-P Fryns, J Chelly, H-H Ropers, C Moraine, B C J Hamel, S Briault ............................................................................................................................... J Med Genet 2005;42:780–786. doi: 10.1136/jmg.2004.029439 lymphoblastoid cell lines (family N42) that were established Truncating mutations were found in the PHF8 gene (encoding from peripheral lymphocytes using standard protocols. the PHD finger protein 8) in two unrelated families with X linked mental retardation (XLMR) associated with cleft lip/ palate (MIM 300263). Expression studies showed that this Fluorescence in situ hybridisation (FISH) BACs on chromosome Xp11.21 were selected from Ensembl gene is ubiquitously transcribed, with strong expression of database (http://www.ensembl.org) and the UCSC genome the mouse orthologue Phf8 in embryonic and adult brain browser (http://genome.ucsc.edu) and obtained from the structures. The coded PHF8 protein harbours two functional CHORI Institute (http://bacpac.chori.org). Hybridisation domains, a PHD finger and a JmjC (Jumonji-like C terminus) experiments were carried out as previously described.12 domain, implicating it in transcriptional regulation and chromatin remodelling. The association of XLMR and cleft lip/palate in these patients with mutations in PHF8 suggests Mutation analysis of PHF8 Polymerase chain reaction (PCR) was carried out in 50 ml an important function of PHF8 in midline formation and in the reaction volumes containing 100 ng of genomic DNA from development of cognitive abilities, and links this gene to the patients, 10 pM of each primer, 1.25 mM of dNTPs, 0.5 U XLMR associated with cleft lip/palate.
    [Show full text]
  • Prox1regulates the Subtype-Specific Development of Caudal Ganglionic
    The Journal of Neuroscience, September 16, 2015 • 35(37):12869–12889 • 12869 Development/Plasticity/Repair Prox1 Regulates the Subtype-Specific Development of Caudal Ganglionic Eminence-Derived GABAergic Cortical Interneurons X Goichi Miyoshi,1 Allison Young,1 Timothy Petros,1 Theofanis Karayannis,1 Melissa McKenzie Chang,1 Alfonso Lavado,2 Tomohiko Iwano,3 Miho Nakajima,4 Hiroki Taniguchi,5 Z. Josh Huang,5 XNathaniel Heintz,4 Guillermo Oliver,2 Fumio Matsuzaki,3 Robert P. Machold,1 and Gord Fishell1 1Department of Neuroscience and Physiology, NYU Neuroscience Institute, Smilow Research Center, New York University School of Medicine, New York, New York 10016, 2Department of Genetics & Tumor Cell Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, 3Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan, 4Laboratory of Molecular Biology, Howard Hughes Medical Institute, GENSAT Project, The Rockefeller University, New York, New York 10065, and 5Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 Neurogliaform (RELNϩ) and bipolar (VIPϩ) GABAergic interneurons of the mammalian cerebral cortex provide critical inhibition locally within the superficial layers. While these subtypes are known to originate from the embryonic caudal ganglionic eminence (CGE), the specific genetic programs that direct their positioning, maturation, and integration into the cortical network have not been eluci- dated. Here, we report that in mice expression of the transcription factor Prox1 is selectively maintained in postmitotic CGE-derived cortical interneuron precursors and that loss of Prox1 impairs the integration of these cells into superficial layers. Moreover, Prox1 differentially regulates the postnatal maturation of each specific subtype originating from the CGE (RELN, Calb2/VIP, and VIP).
    [Show full text]
  • Enzyme DHRS7
    Toward the identification of a function of the “orphan” enzyme DHRS7 Inauguraldissertation zur Erlangung der Würde eines Doktors der Philosophie vorgelegt der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel von Selene Araya, aus Lugano, Tessin Basel, 2018 Originaldokument gespeichert auf dem Dokumentenserver der Universität Basel edoc.unibas.ch Genehmigt von der Philosophisch-Naturwissenschaftlichen Fakultät auf Antrag von Prof. Dr. Alex Odermatt (Fakultätsverantwortlicher) und Prof. Dr. Michael Arand (Korreferent) Basel, den 26.6.2018 ________________________ Dekan Prof. Dr. Martin Spiess I. List of Abbreviations 3α/βAdiol 3α/β-Androstanediol (5α-Androstane-3α/β,17β-diol) 3α/βHSD 3α/β-hydroxysteroid dehydrogenase 17β-HSD 17β-Hydroxysteroid Dehydrogenase 17αOHProg 17α-Hydroxyprogesterone 20α/βOHProg 20α/β-Hydroxyprogesterone 17α,20α/βdiOHProg 20α/βdihydroxyprogesterone ADT Androgen deprivation therapy ANOVA Analysis of variance AR Androgen Receptor AKR Aldo-Keto Reductase ATCC American Type Culture Collection CAM Cell Adhesion Molecule CYP Cytochrome P450 CBR1 Carbonyl reductase 1 CRPC Castration resistant prostate cancer Ct-value Cycle threshold-value DHRS7 (B/C) Dehydrogenase/Reductase Short Chain Dehydrogenase Family Member 7 (B/C) DHEA Dehydroepiandrosterone DHP Dehydroprogesterone DHT 5α-Dihydrotestosterone DMEM Dulbecco's Modified Eagle's Medium DMSO Dimethyl Sulfoxide DTT Dithiothreitol E1 Estrone E2 Estradiol ECM Extracellular Membrane EDTA Ethylenediaminetetraacetic acid EMT Epithelial-mesenchymal transition ER Endoplasmic Reticulum ERα/β Estrogen Receptor α/β FBS Fetal Bovine Serum 3 FDR False discovery rate FGF Fibroblast growth factor HEPES 4-(2-Hydroxyethyl)-1-Piperazineethanesulfonic Acid HMDB Human Metabolome Database HPLC High Performance Liquid Chromatography HSD Hydroxysteroid Dehydrogenase IC50 Half-Maximal Inhibitory Concentration LNCaP Lymph node carcinoma of the prostate mRNA Messenger Ribonucleic Acid n.d.
    [Show full text]