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The Inhibitor of Growth Protein 5 (ING5) Depends on INCA1 as a Co-Factor for Its Antiproliferative Effects

The proteins of the Inhibitor of Growth (ING) family are involved in multiple cellular functions such as cell cycle regulation, apoptosis, and chromatin remodeling. For ING5, its actual role in growth suppression and the necessary partners are not known. In a yeast-two-hybrid approach with human bone marrow derived cDNA, we identified ING5 as well as several other proteins as interaction partners of Inhibitor of cyclin A1 (INCA1) that we previously characterized as a novel interaction partner of cyclin A1/CDK2. ING5 expression in leukemic AML blasts was severely reduced compared to normal bone marrow. In line, ING5 inhibited bone marrow colony formation upon retroviral transduction. However, Inca12/2 bone marrow colony formation was not suppressed by ING5. In murine embryonic fibroblast (MEF) cells from Inca1+/+ and Inca12/2 mice, overexpression of ING5 suppressed cell proliferation only in the presence of INCA1, while ING5 had no effect in Inca12/2 MEFs. ING5 overexpression induced a delay in S-phase progression, which required INCA1. Finally, ING5 overexpression enhanced Fas-induced apoptosis in Inca1+/+ MEFs, while Inca12/2 MEFs were protected from Fas antibody-induced apoptosis. Taken together, these results indicate that ING5 is a growth suppressor with suppressed expression in AML whose functions depend on its interaction with INCA1.  

Titel: The Inhibitor of Growth Protein 5 (ING5) Depends on INCA1 as a Co-Factor for Its Antiproliferative Effects
Verfasser: Zhang, Feng
Bäumer, Nicole GND
Rode, Miriam
Ji, Ping
Zhang, Tao
Berdel, Wolfgang E. GND
Müller-Tidow, Carsten GND
Organisation: FB 05: Medizinische Fakultät
Dokumenttyp: Artikel
Medientyp: Text
Erscheinungsdatum: 05.07.2011
Publikation in MIAMI: 20.02.2013
Datum der letzten Änderung: 16.04.2019
Quelle: PLoS ONE 6 (2011) 7, e21505.
Fachgebiete: Medizin und Gesundheit
Lizenz: CC BY 2.5
Sprache: Englisch
Anmerkungen: Finanziert durch den Open-Access-Publikationsfonds 2011/2012 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format: PDF-Dokument
URN: urn:nbn:de:hbz:6-87379490442
DOI: 10.1371/journal.pone.0021505