TY - JOUR AU - Prange, K.H.M. AU - Mandoli, A. AU - Kuznetsova, T. AU - Wang, S. AU - Sotoca, A.M. AU - Marneth, A.E. AU - Van der Reijden, B.A. AU - Stunnenberg, H. AU - Martens, J.H.A. PY - 2017 UR - https://hdl.handle.net/2066/168892 TI - MLL-AF9 and MLL-AF4 oncofusion proteins bind a distinct enhancer repertoire and target the RUNX1 program in 11q23 acute myeloid leukemia EP - 11 SN - 0950-9232 SP - 1 JF - Oncogene PS - 11 p. DO - https://doi.org/10.1038/onc.2016.488 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/168892/168892.pdf?sequence=1 ER - TY - JOUR AU - van den Boom, V. AU - Maat, H. AU - Geugien, M. AU - Lopez, A.R. AU - Sotoca, A.M. AU - Jaques, J. AU - Brouwers-Vos, A.Z. AU - Fusetti, F. AU - Groen, R.W.J. AU - Yuan, H.P. AU - Martens, A.C.M. AU - Stunnenberg, H.G. AU - Vellenga, E. AU - Martens, J.H.A. AU - Schuringa, J.J. PY - 2016 UR - https://hdl.handle.net/2066/156956 TI - Non-canonical PRC1.1 Targets Active Genes Independent of H3K27me3 and Is Essential for Leukemogenesis EP - 346 SN - 2211-1247 IS - iss. 2 SP - 332 JF - Cell Reports VL - vol. 14 DO - https://doi.org/10.1016/j.celrep.2015.12.034 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/156956/156956.pdf?sequence=1 ER - TY - JOUR AU - Sotoca Covaleda, A.M. AU - Prange, K.H.M. AU - Reijnders, B. AU - Mandoli, A. AU - Nguyen, L.N. AU - Stunnenberg, H.G. AU - Martens, J.H.A. PY - 2015 UR - https://hdl.handle.net/2066/145003 TI - The oncofusion protein FUS-ERG targets key hematopoietic regulators and modulates the all-trans retinoic acid signaling pathway in t(16;21) acute myeloid leukemia EP - 1976 SN - 0950-9232 SP - 1965 JF - Oncogene VL - vol. 35 DO - https://doi.org/10.1038/onc.2015.261 ER - TY - JOUR AU - Wingens, M. AU - Jacobs-Oomen, S. AU - Woning, S.P. van der AU - Stortelers, C. AU - Zoelen, E.J.J. van PY - 2006 UR - https://hdl.handle.net/2066/35868 TI - Epidermal growth factor mutant with wild-type affinity for both ErbB1 and ErbB3 EP - 4710 SN - 0006-2960 IS - iss. 14 SP - 4703 JF - Biochemistry VL - vol. 45 ER - TY - JOUR AU - Woning, S.P. van der AU - Rotterdam, W. van AU - Nabuurs, S.B. AU - Venselaar, H. AU - Jacobs-Oomen, S. AU - Wingens, M. AU - Vriend, G. AU - Stortelers, C. AU - Zoelen, E.J.J. van PY - 2006 UR - https://hdl.handle.net/2066/35633 AB - Epidermal growth factor (EGF)-like growth factors bind their ErbB receptors in a highly selective manner, but the molecular basis for this specificity is poorly understood. We have previously shown that certain residues in human EGF (Ser(2)-Asp(3)) and TGFalpha (Glu(26)) are not essential for their binding to ErbB1 but prevent binding to ErbB3 and ErbB4. In the present study, we have used a phage display approach to affinity-optimize the C-terminal linear region of EGF-like growth factors for binding to each ErbB receptor and thereby shown that Arg(45) in EGF impairs binding to both ErbB3 and ErbB4. By omitting all these so-called negative constraints from EGF, we designed a ligand designated panerbin that binds ErbB1, ErbB3, and ErbB4 with similarly high affinity as their wild-type ligands. Homology models, based on the known crystal structure of TGFalpha-bound ErbB1, showed that panerbin is able to bind ErbB1, ErbB3, and ErbB4 in a highly similar manner with respect to position and number of interaction sites. Upon in silico introduction of the experimentally known negative constraints into panerbin, we found that Arg(45) induced local charge repulsion and Glu(26) induced steric hindrance in a receptor-specific manner, whereas Ser(2)-Asp(3) impaired binding due to a disordered conformation. Furthermore, radiolabeled panerbin was used to quantify the level of all three receptors on human breast cancer cells in a single radioreceptor assay. It is concluded that the ErbB specificity of EGF-like growth factors primarily results from the presence of a limited number of residues that impair the unintended interaction with other ErbB receptors. TI - Negative constraints underlie the ErbB specificity of epidermal growth factor-like ligands EP - 40040 SN - 1083-351X IS - iss. 52 SP - 40033 JF - Journal of Biological Chemistry VL - vol. 281 DO - https://doi.org/10.1074/jbc.M603168200 ER - TY - JOUR AU - Vaes, B.L.T. AU - Dechering, K.J. AU - Someren, E.P. van AU - Hendriks, J.M. AU - Ven, C.J. van de AU - Feijen, A. AU - Mummery, C.L. AU - Reinders, M.J. AU - Olijve, W. AU - Zoelen, E.J.J. van AU - Steegenga, W.T. PY - 2005 UR - https://hdl.handle.net/2066/32739 AB - Wnt signaling has been implicated in regulating bone formation by controlling osteoblast proliferation and function. Although stabilization of beta-catenin by Wnt has been shown to increase alkaline phosphatase expression and osteoblast differentiation, the precise role of Wnt signaling during the process of osteoblast differentiation is largely unknown. In this study, we used microarray technology to investigate expression regulation of Wnt signaling components during in vitro osteoblast differentiation. Expression was analyzed during bone morphogenetic protein 2 (BMP2)-induced osteoblast differentiation of murine C2C12 and MC3T3 cells and data were compared with expression in BMP2-treated NIH3T3 fibroblasts. During osteoblast differentiation, particularly strong expression regulation of the Wnt antagonists Sfrp2 (secreted frizzled related protein 2) and Wif1 (Wnt inhibitory factor 1) was observed in the late phase of differentiation. In situ expression analysis in murine tail vertebrae supported Wif1 expression during late phase bone cell differentiation, since Wif1 was found to be expressed in vivo in trabecular, but not in cortical bone. We further analyzed the effects of continuous activation of Wnt signaling by lithium chloride and observed that osteoblast differentiation was reduced, as measured by expression of osteoblast marker genes encoding alkaline phosphatase, osteocalcin, and osterix, as well as by the amount of calcium release. Taken together, our data indicate that endogenous expression of Wnt antagonists by osteoblasts provides a negative Wnt feedback loop which is essential in controlling osteoblast maturation. TI - Microarray analysis reveals expression regulation of Wnt antagonists in differentiating osteoblasts EP - 811 SN - 8756-3282 IS - iss. 5 SP - 803 JF - Bone VL - vol. 36 DO - https://doi.org/10.1016/j.bone.2005.02.001 ER - TY - JOUR AU - Jong, D.S. de AU - Vaes, B.L.T. AU - Dechering, K.J. AU - Feijen, A. AU - Hendriks, J.M. AU - Wehrens, H.R.M.J. AU - Mummery, C.L. AU - Zoelen, E.J.J. van AU - Olijve, W. AU - Steegenga, W.T. PY - 2004 UR - https://hdl.handle.net/2066/58213 AB - Key regulatory components of the BMP-induced osteoblast differentiation cascade remain to be established. Microarray and subsequent expression analyses in mice identified two transcription factors, Hey1 and Tcf7, with in vitro and in vivo expression characteristics very similar to Cbfa1. Transfection studies suggest that Tcf7 modulates BMP2-induced osteoblast differentiation. This study contributes to a better definition of the onset of BMP-induced osteoblast differentiation. INTRODUCTION: Elucidation of the genetic cascade guiding mesenchymal stem cells to become osteoblasts is of extreme importance for improving the treatment of bone-related diseases such as osteoporosis. The aim of this study was to identify regulators of the early phases of bone morphogenetic protein (BMP)2-induced osteoblast differentiation. MATERIALS AND METHODS: Osteoblast differentiation of mouse C2C12 cells was induced by treatment with BMP2, and regulation of gene expression was studied during the subsequent 24 h using high-density microarrays. The regulated genes were grouped by means of model-based clustering, and protein functions were assigned. Real-time quantitative RT-PCR analysis was used to validate BMP2-induced gene expression patterns in C2C12 cells. Osteoblast specificity was studied by comparing these expression patterns with those in C3H10T1/2 and NIH3T3 cells under similar conditions. In situ hybridization of mRNA in embryos at embryonic day (E)14.5 and E16.5 of gestation and on newborn mouse tails were used to study in vivo expression patterns. Cells constitutively expressing the regulated gene Tcf7 were used to investigate its influence on BMP-induced osteoblast differentiation. RESULTS AND CONCLUSIONS: A total of 184 genes and expressed sequence tags (ESTs) were differentially expressed in the first 24 h after BMP2 treatment and grouped in subsets of immediate early, intermediate early, and late early response genes. Signal transduction regulatory factors mainly represented the subset of immediate early genes. Regulation of expression of these genes was direct, independent of de novo protein synthesis and independent of the cell type studied. The intermediate early and late early genes consisted primarily of genes related to processes that modulate morphology, basement membrane formation, and synthesis of extracellular calcified matrix. The late early genes require de novo protein synthesis and show osteoblast specificity. In vivo and in vitro experiments showed that the transcription factors Hey1 and Tcf7 exhibited expression characteristics and cell type specificity very similar to those of the osteoblast specific transcription factor Cbfa1, and constitutive expression of Tcf7 in C2C12 cells differentially regulated osteoblast differentiation marker genes. TI - Identification of novel regulators associated with early-phase osteoblast differentiation. EP - 958 SN - 0884-0431 IS - iss. 6 SP - 947 JF - Journal of Bone and Mineral Research VL - vol. 19 DO - https://doi.org/10.1359/JBMR.040216 ER - TY - JOUR AU - Jong, D.S. de AU - Steegenga, W.T. AU - Hendriks, J.M. AU - Zoelen, E.J.J. van AU - Olijve, W. AU - Dechering, K.J. PY - 2004 UR - https://hdl.handle.net/2066/57750 AB - The bone morphogenetic protein (BMP)-induced Smad signal transduction pathway is an important positive regulator of osteoblast differentiation. BMP and other members of the transforming growth factor-beta (TGF-beta) family have distinct effects on osteoblast differentiation, depending on cell type and cell differentiation status. In C2C12 mesenchymal cells, BMP-induced osteoblast differentiation can be blocked by TGF-beta. In a search for key regulators of osteoblast differentiation we have used microarray analysis to identify genes which are differentially regulated by BMP2 and TGF-beta. Within the first 24 h following the onset of differentiation, 61 BMP2-regulated genes were identified of which the BMP2 effect was counteracted by TGF-beta. The majority of these differentially expressed transcripts are related to signal transduction. Notably, our data show that three Notch signal transduction pathway genes, Lfng, Hey1, and Hes1, are differentially regulated by BMP2 and TGF-beta. This suggests that these genes might function as the focal point for interaction of Smad and Notch signaling during osteoblast differentiation. TI - Regulation of Notch signaling genes during BMP2-induced differentiation of osteoblast precursor cells. EP - 107 SN - 0006-291X IS - iss. 1 SP - 100 JF - Biochemical and Biophysical Research Communications VL - vol. 320 DO - https://doi.org/10.1016/j.bbrc.2004.05.150 ER - TY - JOUR AU - Stortelers, C. AU - Woning, S.P. van der AU - Jacobs-Oomen, S. AU - Wingens, M. AU - Zoelen, E.J.J. van PY - 2003 UR - https://hdl.handle.net/2066/129304 TI - Selective formation of ErbB-2/ErbB-3 heterodimers depends on the ErbB-3 affinity of epidermal growth factor-like ligands EP - 12063 SN - 1083-351X SP - 12055 JF - Journal of Biological Chemistry VL - vol. 278 DO - https://doi.org/10.1074/jbc.M211948200 ER - TY - JOUR AU - Wingens, M. AU - Walma, T. AU - Ingen, H. van AU - Stortelers, C. AU - Leeuwen, J.E.M. van AU - Zoelen, E.J.J. van AU - Vuister, G.W. PY - 2003 UR - https://hdl.handle.net/2066/79479 TI - Structural analysis of an epidermal growth factor/transforming growth factor-alpha chimera with unique ErbB binding specificity EP - 39123 SN - 1083-351X IS - iss. 40 SP - 39114 JF - Journal of Biological Chemistry VL - vol. 278 DO - https://doi.org/10.1074/jbc.M305603200 ER - TY - JOUR AU - Joosten, P.H.L.J. AU - Toepoel, M. AU - Oosterhout, D. van AU - Afink, G.B. AU - Zoelen, E.J.J. van PY - 2002 UR - https://hdl.handle.net/2066/129306 TI - A regulating element essential for PDGRFA transcription is recognized by neural tube defect-associated PRX homeobox transcription factors EP - 260 SN - 0925-4439 SP - 254 JF - Biochimica et Biophysica Acta. Molecular Basis of Disease VL - vol. 1588 DO - https://doi.org/10.1016/S0925-4439(02)00175-8 ER - TY - JOUR AU - Vaes, B.L.T. AU - Dechering, K.J. AU - Feijen, A. AU - Hendriks, J.M.A. AU - Lefevre, C. AU - Mummery, C.L. AU - Olijve, W. AU - Zoelen, E.J.J. van AU - Steegenga, W.T. PY - 2002 UR - https://hdl.handle.net/2066/129307 TI - Comprehensive microarray analysis of bone morphogenetic protein 2-induced osteoblast differentiation resulting in the identification of novel markers for bone development EP - 2118 SN - 0884-0431 SP - 2106 JF - Journal of Bone and Mineral Research VL - vol. 17 DO - https://doi.org/10.1359/jbmr.2002.17.12.2106 ER - TY - JOUR AU - Stortelers, C. AU - Poll, M.L.M. van de AU - Lenferink, A.E.G. AU - Gadellaa, M.M. AU - Zoelen, C. van AU - Zoelen, E.J.J. van PY - 2002 UR - https://hdl.handle.net/2066/129310 TI - Epidermal growth factor contains both positive and negative determinants for interaction with ErbB2/ErbB-3 heterodimers EP - 4301 SN - 0006-2960 SP - 4292 JF - Biochemistry VL - vol. 41 DO - https://doi.org/10.1021/bi012016n ER - TY - JOUR AU - Stortelers, C. AU - Souriau, C. AU - Liempt, E. van AU - Poll, M.L.M. van de AU - Zoelen, E.J.J. van PY - 2002 UR - https://hdl.handle.net/2066/129314 TI - Role of the N-terminus of epidermal growth factor in ErbB-2/ErbB-3 binding studied by phage display EP - 8741 SN - 0006-2960 SP - 8732 JF - Biochemistry VL - vol. 41 DO - https://doi.org/10.1021/bi025878c ER - TY - JOUR AU - Harks, G.A. AU - Roos, A.D.G. de AU - Peters, P.H.J. AU - Haan, L. de AU - Brouwer, A.P.M. de AU - Ypey, D.L. AU - Zoelen, E.J.J. van AU - Theuvenet, A.P.R. PY - 2001 UR - https://hdl.handle.net/2066/185645 AB - The effect of fenamates on gap junctional intercellular communication was investigated in monolayers of normal rat kidney (NRK) fibroblasts and of SKHep1 cells overexpressing the gap junction protein connexin43 (Cx43). Using two different methods to study gap junctional intercellular communication, single electrode voltage-clamp step response measurements and dye microinjection, we show that fenamates are reversible blockers of Cx43-mediated intercellular communication. After adding fenamates to a confluent monolayer of electrically coupled NRK fibroblasts, the voltage step-induced capacitive current transient changed from a transient characteristic for charging multiple coupled cell capacitances to one characteristic for a single cell in isolation. The capacitance of completely uncoupled cells was 19.7 +/- 1.0 pF (mean +/- S.E.M.; n = 11). Junctional conductance between the patched cell and the surrounding cells in the monolayer changed from >140.7 +/- 9.6 nS (mean +/- S.E.M.; n = 14) to <1.4 +/- 0.4 nS (mean +/- S.E.M.; n = 11) after uncoupling. Electrical coupling could be restored to >51.8 +/- 4.2 nS (mean +/- S.E.M.; n = 11) by washout of the fenamates. Voltage-clamp step response measurements showed that the potency of fenamates in inhibiting electrical coupling decreases in the order meclofenamic acid > niflumic acid > flufenamic acid. The half-maximal concentration determined by dye-coupling experiments was 25 and 40 microM for meclofenamic acid and flufenamic acid, respectively. Inhibition of gap junctional communication by fenamates did not involve changes in intracellular calcium or pH, and was unrelated to protein kinase C activity or an inhibition of cyclooxygenase activity. Voltage-clamp step response measurements in confluent monolayers of SKHep1 cells that had been stably transfected with Cx43 revealed that fenamates are potent blockers of Cx43-mediated intercellular communication. In conclusion, fenamates represent a novel class of reversible gap junction blockers that can be used to study the role of Cx43-mediated gap junctional intercellular communication in biological processes. TI - Fenamates: a novel class of reversible gap junction blockers. EP - 1041 SN - 0022-3565 IS - iss. 3 SP - 1033 JF - Journal of Pharmacology and Experimental Therapeutics VL - vol. 298 ER - TY - JOUR AU - Wijngaard, A. van de AU - Mulder, W.R. AU - Dijkema, R. AU - Boersma, C.J.C. AU - Mosselman, S. AU - Zoelen, E.J.J. van AU - Olijve, W. PY - 2000 UR - https://hdl.handle.net/2066/129324 TI - Antiestrogens specifically upregulate bone morphogenetic protein-4 promoter activity in human osteoblastic cells EP - 633 SN - 0888-8809 SP - 623 JF - Molecular Endocrinology VL - vol. 14 DO - https://doi.org/10.1210/me.14.5.623 ER - TY - JOUR AU - Poll, M.L.M. van de AU - Rotterdam, W. van AU - Gadellaa, M.M. AU - Stortelers, C. AU - Vught, M.J.H. van AU - Zoelen, E.J.J. van PY - 2000 UR - https://hdl.handle.net/2066/129328 TI - Non-linear antigenic regions in epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) studied by EGF-TGFalpha chimaeras EP - 274 SN - 0264-6021 SP - 267 JF - Biochemical Journal VL - vol. 349 DO - https://doi.org/10.1042/0264-6021:3490267 ER - TY - JOUR AU - Lenferink, A.E.G. AU - Zoelen, E.J.J. van AU - Vugt, M. van AU - Grothe, S. AU - Rotterdam, W. van AU - Poll, M.L.M. van de AU - O'Connor-McCourt, M.D. PY - 2000 UR - https://hdl.handle.net/2066/129332 TI - Superagonistic activation of ErbB-1 by EGF-related growth factors with enhanced association and dissociation rate constants EP - 26753 SN - 1083-351X SP - 26748 JF - Journal of Biological Chemistry VL - vol. 275 ER - TY - JOUR AU - Zoelen, E.J.J. van AU - Stortelers, C. AU - Lenferink, A.E.G. AU - Poll, M.L.M. van de PY - 2000 UR - https://hdl.handle.net/2066/129334 TI - The EGF domain: requirements for binding to receptors of the ErbB familly EP - 131 SN - 0083-6729 SP - 99 JF - Vitamins and Hormones VL - vol. 59 ER - TY - JOUR AU - Lahaye, D.H.T.P. AU - Camps, M. AU - Zoelen, E.J.J. van PY - 1999 UR - https://hdl.handle.net/2066/129335 TI - Central role of epidermal growth factor (EGF) receptor density in anchorage-independent growth of normal rad kidney cells EP - 260 SN - 1873-3468 SP - 256 JF - FEBS Letters VL - vol. 446 DO - https://doi.org/10.1016/S0014-5793(99)00216-1 ER - TY - JOUR AU - Boersma, C.J.C. AU - Bloemen, M. AU - Hendriks, J.M.A. AU - Berkel, E.A.T. van AU - Olijve, W. AU - Zoelen, E.J.J. van PY - 1999 UR - https://hdl.handle.net/2066/129340 TI - Homeobox proteins as signal transfuction intermediates in regulation of NCAM expression by recombinant human bone morphogenetic protein-2 in osteoblast-like cells EP - 124 SN - 1522-4724 SP - 117 JF - Molecular Cell Biology Research Communications VL - vol. 1 ER - TY - JOUR AU - Lahaye, D.H.T.P. AU - Walboomers, X.F. AU - Peters, P.H.J. AU - Theuvenet, A.P.R. AU - Zoelen, E.J.J. van PY - 1999 UR - https://hdl.handle.net/2066/129343 TI - Phenotypic transformation of normal rad kidney fibroblasts by endothelin-1. Different mode of action from lysophosphatidic acid, bradykinin, and prostaglandin F2alpha EP - 118 SN - 0167-4889 SP - 107 JF - Biochimica et Biophysica Acta. Molecular Cell Research VL - vol. 1449 DO - https://doi.org/10.1016/S0167-4889(99)00002-6 ER - TY - JOUR AU - Joosten, P.H.L.J. AU - Hol, F.A. AU - Beersum, S.E.C. van AU - Peters, H. AU - Hamel, B.C.J. AU - Afink, G.B. AU - Zoelen, E.J.J. van AU - Mariman, E.C.M. PY - 1998 UR - https://hdl.handle.net/2066/120796 TI - Altered regulation of PDGFRa transcription in vitro by spina bifida associated mutant Pax1 proteins EP - 14463 SN - 0027-8424 SP - 14459 JF - Proceedings of the National Academy of Sciences USA VL - vol. 95 PS - 5 p. DO - https://doi.org/10.1073/pnas.95.24.14459 ER - TY - JOUR AU - Roos, A.D.G. de AU - Willems, P.H.G.M. AU - Peters, P.H.J. AU - Zoelen, E.J.J. van AU - Theuvenet, A.P.R. PY - 1997 UR - https://hdl.handle.net/2066/222850 TI - Synchronized calcium spiking resulting from spontaneous calcium action potentials in monolayers of NRK fibroblasts EP - 207 SN - 0143-4160 SP - 195 JF - Cell Calcium VL - vol. 22 DO - https://doi.org/10.1016/S0143-4160(97)90013-0 ER - TY - JOUR AU - Roos, A.D.G. de AU - Willems, P.H.G.M. AU - Zoelen, E.J.J. van AU - Theuvenet, A.P.R. PY - 1997 UR - https://hdl.handle.net/2066/222849 TI - Synchronized Ca2+ signaling by intercellular propagation of Ca2+ action potentials in NRK fibroblasts EP - C1907 SN - 0002-9513 SP - C1900 JF - American Journal of Physiology VL - vol. 273 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/222849/222849.pdf?sequence=1 ER - TY - JOUR AU - Wijngaard, A. van de AU - Olde Weghuis, D.E.M. AU - Boersma, C.J.C. AU - Zoelen, E.J.J. van AU - Geurts van Kessel, A.H.M. AU - Olijve, W. PY - 1995 UR - https://hdl.handle.net/2066/197651 TI - Fine mapping of the human bone morphogenetic protein-4 (BMP-4) gene to chromosome 14q22-q23 by in situ hybridization EP - 560 SN - 0888-7543 SP - 559 JF - Genomics : International Journal of Gene Mapping and Nucleotide Sequencing Emphasizing Analyses of the Human and Other Complex Genomes VL - vol. 27 DO - https://doi.org/10.1006/geno.1995.1096 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/197651/197651.pdf?sequence=1 ER - TY - JOUR AU - Poll, M.L.M. van de AU - Lenferink, A.E.G. AU - Vugt, A.H.M. van AU - Jacobs, J.J.L. AU - Janssen, J.W.H. AU - Joldersma, M. AU - Zoelen, E.J.J. van PY - 1995 UR - https://hdl.handle.net/2066/216426 TI - A single amino acid exchange, Arg 45 to Ala, generates an epidermal growth facor (EGF) mutant with high affinity for the chicken EGF receptor EP - 22343 SN - 1083-351X SP - 22337 JF - Journal of Biological Chemistry VL - vol. 270 DO - https://doi.org/10.1074/jbc.270.38.22337 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/216426/216426.pdf?sequence=1 ER -