Abstract

We have cloned the ING family genes (p33ING2, p47ING3, p29ING4, and p29ING5). ING family genes have a PHD-finger motif, which is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in chromatin-mediated transcriptional regulation. The function of this domain is not yet known, but in analogy with the LIM domain, it could be involved in protein-protein interactions and necessary for the assembly or activity of multicomponent complexes involved in transcriptional activation or repression. The p33ING1 protein is a regulator of cell cycle, senescence, and apoptosis. Three alternatively spliced transcripts of p33ING1 encode p47ING1a, p33ING2/ING1L. Unlike p33ING1b, p33ING2 is induced by the DNA-damaging agents etoposide and neocarzinostatin. p33ING1b and p22ING2 negatively regulate cell growth and survival in a p53-dependent manner through the induction of G1-phase cell-cycle arrest and apoptosis. p33ING2 strongly enhances the transcriptional-transactivation activity of p53. Furthermore, p33ING2 expression increases the acetylation of p53 at Lys-382. Taken together, p33ING2 is a DNA damage-inducible gene that negatively regulates cell proliferation through the activation of p53 by enhancing its acetylation. p47ING3, p29ING4, and p29ING5 each regulate p53 transcriptional function by chromatin remodeling.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC005795-08
Application #
6761643
Study Section
(LHC)
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2002
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Solomon, Hilla; Dinowitz, Nathan; Pateras, Ioannis S et al. (2018) Mutant p53 gain of function underlies high expression levels of colorectal cancer stem cells markers. Oncogene 37:1669-1684
Cooks, Tomer; Harris, Curtis C (2014) p53 mutations and inflammation-associated cancer are linked through TNF signaling. Mol Cell 56:611-2
Kumamoto, Kensuke; Fujita, Kaori; Kurotani, Reiko et al. (2009) ING2 is upregulated in colon cancer and increases invasion by enhanced MMP13 expression. Int J Cancer 125:1306-15
Unoki, Motoko; Kumamoto, Kensuke; Robles, Ana I et al. (2008) A novel ING2 isoform, ING2b, synergizes with ING2a to prevent cell cycle arrest and apoptosis. FEBS Lett 582:3868-74
Kumamoto, Kensuke; Spillare, Elisa A; Fujita, Kaori et al. (2008) Nutlin-3a activates p53 to both down-regulate inhibitor of growth 2 and up-regulate mir-34a, mir-34b, and mir-34c expression, and induce senescence. Cancer Res 68:3193-203
Shen, Jiang-Cheng; Unoki, Motoko; Ythier, Damien et al. (2007) Inhibitor of growth 4 suppresses cell spreading and cell migration by interacting with a novel binding partner, liprin alpha1. Cancer Res 67:2552-8
Yang, Qin; Zhang, Ran; Horikawa, Izumi et al. (2007) Functional diversity of human protection of telomeres 1 isoforms in telomere protection and cellular senescence. Cancer Res 67:11677-86
Hussain, S P; Schwank, J; Staib, F et al. (2007) TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer. Oncogene 26:2166-76
Koshiji, Minori; Kumamoto, Kensuke; Morimura, Keiichirou et al. (2007) Correlation of N-myc downstream-regulated gene 1 expression with clinical outcomes of colorectal cancer patients of different race/ethnicity. World J Gastroenterol 13:2803-10
Okano, Tetsuya; Gemma, Akihiko; Hosoya, Yoko et al. (2006) Alterations in novel candidate tumor suppressor genes, ING1 and ING2 in human lung cancer. Oncol Rep 15:545-9

Showing the most recent 10 out of 35 publications