Members of a family of JmjC domain-containing oncoproteins immortalize embryonic fibroblasts via a JmjC domain-dependent process
| Autor: | Susan E. Bear, Sotirios C. Kampranis, Oksana B. Serebrennikova, Alexandros Tzatsos, Raymond Pfau, Philip N. Tsichlis |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Senescence
Blotting Western Molecular Sequence Data Mutant KDM2A KDM2B Lymphoma T-Cell Retinoblastoma Protein Mice Histone H3 Animals Amino Acid Sequence Gene Oncogene Proteins Gene knockdown Multidisciplinary biology Fibroblasts Biological Sciences Provirus Blotting Northern Cell Transformation Viral Embryo Mammalian Molecular biology Rats Inbred F344 Rats Cell Transformation Neoplastic Animals Newborn biology.protein Moloney murine leukemia virus Tumor Suppressor Protein p53 |
| Zdroj: | Proceedings of the National Academy of Sciences. 105:1907-1912 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0711865105 |
| Popis: | A common integration site, cloned from MoMuLV-induced rat T cell lymphomas, was mapped immediately upstream of Not dead yet-1 ( Ndy1 )/ KDM2B , a gene expressed primarily in testis, spleen, and thymus, that is also known as FBXL10 or JHDM1B. Ndy1 encodes a nuclear, chromatin-associated protein that harbors Jumonji C (JmjC), CXXC, PHD, proline-rich, F-box, and leucine-rich repeat domains. Ndy1 and its homolog Ndy2/KDM2A ( FBXL11 or JHDM1A ), which is also a target of provirus integration in retrovirus-induced lymphomas, encode proteins that were recently shown to possess Jumonji C-dependent histone H3 K36 dimethyl-demethylase or histone H3 K4 trimethyl-demethylase activities. Here, we show that mouse embryo fibroblasts engineered to express Ndy1 or Ndy2 undergo immortalization in the absence of replicative senescence via a JmjC domain-dependent process that targets the Rb and p53 pathways. Knockdown of endogenous Ndy1 or expression of JmjC domain mutants of Ndy1 promote senescence, suggesting that Ndy1 is a physiological inhibitor of senescence in dividing cells and that inhibition of senescence depends on histone H3 demethylation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|