Article thumbnail

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

By Feng Zhang, Nicole Bäumer, Miriam Rode, Ping Ji, Tao Zhang, Wolfgang E. Berdel and Carsten Müller-Tidow


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

Topics: Research Article
Publisher: Public Library of Science
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (2003). A novel PHD-finger motif protein, p47ING3, modulates p53-mediated transcription, cell cycle control, and apoptosis.
  2. (2002). Allelic loss and reduced expression of the ING3, a candidate tumor suppressor gene at 7q31, in human head and neck cancers.
  3. (2004). Biological functions of the ING family tumor suppressors.
  4. (1994). Cell cycle control and cancer.
  5. (1997). Characterization of a second human cyclin A that is highly expressed in testis and in several leukemic cell lines.
  6. (1999). Cloning of the cyclin A1 genomic structure and characterization of the promoter region. GC boxes are essential for cell cycle-regulated transcription of the cyclin A1 gene.
  7. (1999). Cyclin A1 expression in leukemia and normal hematopoietic cells.
  8. (1998). Cyclin A1 is required for meiosis in the male mouse.
  9. (2003). Cyclindependent kinase 2 is essential for meiosis but not for mitotic cell division in mice.
  10. (2010). Decreased nuclear expression and increased cytoplasmic expression of ING5 may be linked to tumorigenesis and progression in human head and neck squamous cell carcinoma.
  11. (2002). Different HATS of the ING1 gene family.
  12. (2001). DNA damage-inducible gene p33ING2 negatively regulates cell proliferation through acetylation of p53.
  13. (1999). Functions of cyclin A1 in the cell cycle and its interactions with transcription factor E2F-1 and the Rb family of proteins.
  14. (2006). Grow-ING, Age-ING and Die-ING: ING proteins link cancer, senescence and apoptosis.
  15. (2004). Identification of interaction partners and substrates of the cyclin A1-CDK2 complex.
  16. (2011). ING genes work as tumor suppressor genes in the carcinogenesis of head and neck squamous cell carcinoma.
  17. (2006). ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation.
  18. (2011). Inhibitor of CDK interacting with cyclin A1 (INCA1) regulates proliferation and is repressed by oncogenic signaling.
  19. (2001). Mitotic kinases as regulators of cell division and its checkpoints.
  20. (2008). Molecular architecture of quartet MOZ/MORF histone acetyltransferase complexes.
  21. (2009). Reviewing the current classification of inhibitor of growth family proteins.
  22. (1996). Suppression of the novel growth inhibitor p33ING1 promotes neoplastic transformation.
  23. (2011). The altered expression of ING5 protein is involved in gastric carcinogenesis and subsequent progression.
  24. (1998). The candidate tumour suppressor p33ING1 cooperates with p53 in cell growth control.
  25. (2004). The cyclin A1-CDK2 complex regulates DNA double-strand break repair.
  26. (2005). The fellowships of the INGs.
  27. (2008). The multiple facets of the intra-S checkpoint. Cell Cycle 7: 2315–2320. Interaction between ING5 and INCA1
  28. (2011). The nuclear to cytoplasmic shift of ING5 protein during colorectal carcinogenesis with their distinct links to pathologic behaviors of carcinomas.
  29. (2010). Tumorspecific mutation and downregulation of ING5 detected in oral squamous cell carcinoma.