Runx2 Target Genes

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TABLE 1: Runx2 Target Genes Gene Symbol GenBank Gene ID Annotation – Modified from Dragon Database Cdc27 NM_001256 996 Anaphase promoting complex subunit 3, essential for cell division. DC46 NM_006739 4174 Also known as MCM5, forms a complex with MCM2 and is involved in DNA replication. May have a role in cell division CCDC6 NM_001254 990 Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated. Cdk4 NM_000075 1019 Involved in the control of the cell cycle. Cyclin B2 NM_004701 9133 Essential for the control of the cell cycle at the G2/M (mitosis) transition. Cyclin H NM_001239 902 Involved in cell cycle control and in RNA transcription by RNA polymerase II. Its expression and activity are constant throughout the cell cycle. E2F-6 NM_001952 1876 Inhibitor of E2F-dependent transcription lacks the transcriptional activation and pocket protein binding domains. Controls E2F-dependent genes that are required for cell cycle entry but not progression. GADD45 NM_001924 1647 Binds to proliferating cell nuclear antigen. Might affect PCNA interaction with some CDK (cell division protein kinase) complexes; stimulates DNA excision repair in vitro and inhibits entry of cells into S phase. p18/INK4C NM_078626 1031 Interacts strongly with CDK6, weakly with CDK4. Inhibits cell growth and proliferation with a correlated dependence on endogenous retinoblastoma protein RB. P21/Waf1/CIP1 NM_000389 1026 Important intermediate for p53 function in inhibition of cell proliferation in response to DNA damage. Inhibitor of cyclin-dependent kinase activity and cell cycle progression. RPA3 NM_002947 6119 Absolutely required for simian virus 40 DNA replication in vitro. It participates in a very early step in initiation. RP-A is a single-stranded DNA-binding protein. Smad4/DPC4 NM_005359 4089 Common mediator (co-SMAD) of signal transduction by TGF-beta (transforming growth factor) superfamily. Supports activation of transcription by regulatory SMADs (e.g., SMAD 1, 2, 3, and 5). May act as a tumor suppressor. Smad5 NM_005903 4090 Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD5 is a receptor-regulated SMAD (R-SMAD). VEGF NM_003376 7422 Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis, and induces permeabilization of blood vessels. .

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Jdp2 Downregulates Trp53 Transcription to Promote Leukaemogenesis in the Context of Trp53 Heterozygosity
Oncogene (2013) 32, 397 --402 & 2013 Macmillan Publishers Limited All rights reserved 0950-9232/13 www.nature.com/onc SHORT COMMUNICATION Jdp2 downregulates Trp53 transcription to promote leukaemogenesis in the context of Trp53 heterozygosity L van der Weyden1, AG Rust1,4, RE McIntyre1,4, CD Robles-Espinoza1, M del Castillo Velasco-Herrera1, R Strogantsev2, AC Ferguson-Smith2, S McCarthy1, TM Keane1, MJ Arends3 and DJ Adams1 We performed a genetic screen in mice to identify candidate genes that are associated with leukaemogenesis in the context of Trp53 heterozygosity. To do this we generated Trp53 heterozygous mice carrying the T2/Onc transposon and SB11 transposase alleles to allow transposon-mediated insertional mutagenesis to occur. From the resulting leukaemias/lymphomas that developed in these mice, we identiﬁed nine loci that are potentially associated with tumour formation in the context of Trp53 heterozygosity, including AB041803 and the Jun dimerization protein 2 (Jdp2). We show that Jdp2 transcriptionally regulates the Trp53 promoter, via an atypical AP-1 site, and that Jdp2 expression negatively regulates Trp53 expression levels. This study is the ﬁrst to identify a genetic mechanism for tumour formation in the context of Trp53 heterozygosity. Oncogene (2013) 32, 397--402; doi:10.1038/onc.2012.56; published online 27 February 2012 Keywords: p53; Jdp2; transposon; heterozygosity; lymphoma; mice INTRODUCTION targeted by transposon insertion events leading to upregulated Genetic alterations of TP53 are frequent events in tumourigenesis Jdp2 expression and a decrease in Trp53 expression levels. Further and promote genomic instability, impair apoptosis, and contribute we illustrate that Jdp2 regulates the Trp53 promoter via an atypical to aberrant self-renewal.1--4 The spectrum of mutations that occur AP-1 binding site.
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