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Published on: May 20, 2015
The inhibitor of growth protein 5 (ING5) depends on INCA1 as a co-factor for its antiproliferative effects
Feng Zhang1, Nicole Bäumer, Miriam Rode
1Department of Medicine, Hematology/Oncology, University of Münster, Münster, Germany.
Abstract:
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, Inca1(-/-) bone marrow colony formation was not suppressed by ING5. In murine embryonic fibroblast (MEF) cells from Inca1(+/+) and Inca1(-/-) mice, overexpression of ING5 suppressed cell proliferation only in the presence of INCA1, while ING5 had no effect in Inca1(-/-) MEFs. ING5 overexpression induced a delay in S-phase progression, which required INCA1. Finally, ING5 overexpression enhanced Fas-induced apoptosis in Inca1(+/+) MEFs, while Inca1(-/-) 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.
Insights
Inhibitor of Growth 5 (ING5) suppresses cell growth and promotes apoptosis, but only when interacting with Inhibitor of Cyclin A1 (INCA1). ING5 is downregulated in AML, and its function is dependent on INCA1.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- The Inhibitor of Growth (ING) protein family plays crucial roles in cell cycle regulation, apoptosis, and chromatin remodeling.
- The specific function of ING5 and its interaction partners in growth suppression remain largely uncharacterized.
Purpose of the Study:
- To elucidate the role of ING5 in cell growth suppression and identify its necessary interaction partners.
- To investigate the functional dependence of ING5 on INCA1 in cellular processes.
Main Methods:
- Yeast-two-hybrid screening to identify ING5 interaction partners.
- Retroviral transduction to assess ING5 function in bone marrow colony formation.
- Overexpression studies in murine embryonic fibroblast (MEF) cells (Inca1(+/+) and Inca1(-/-)) to evaluate proliferation, cell cycle progression, and apoptosis.
Main Results:
- ING5 was identified as an interaction partner of INCA1.
- ING5 expression was significantly reduced in acute myeloid leukemia (AML) blasts compared to normal bone marrow.
- ING5 inhibited bone marrow colony formation, but this effect was abolished in Inca1(-/-) cells.
- ING5-mediated suppression of cell proliferation, S-phase delay, and enhancement of Fas-induced apoptosis were dependent on the presence of INCA1.
Conclusions:
- ING5 functions as a growth suppressor, with its activity contingent upon interaction with INCA1.
- The suppressed expression of ING5 in AML suggests a potential role in leukemogenesis.
- INCA1 is essential for mediating the growth-suppressive and apoptosis-inducing functions of ING5.
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