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 in not yet known, but in analogy with the LIM domain, it could be involved in protein-protein interaction 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 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 activation of p53 by enhancing its acetylation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC005795-07
Application #
6558975
Study Section
(LHC)
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2001
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
Spillare, E A; Wang, X W; von Kobbe, C et al. (2006) Redundancy of DNA helicases in p53-mediated apoptosis. Oncogene 25:2119-23

Showing the most recent 10 out of 35 publications