ING4 explained

Inhibitor of growth protein 4 is a protein that in humans is encoded by the ING4 gene.^{[1] [2]}

Function

The protein encoded by this gene is similar to ING1, a tumor suppressor protein that can interact with TP53, inhibit cell growth, and induce apoptosis. This protein contains a PHD-finger, which is a common motif in proteins involved in chromatin remodeling. This protein can bind TP53 and EP300/p300, a component of the histone acetyl transferase complex, suggesting its involvement in the TP53-dependent regulatory pathway. Alternatively spliced transcript variants have been observed, but the biological validity of them has not been determined.

Interactions

ING4 has been shown to interact with EP300, RELA^[3] and P53.^{[1] [4]}

Further reading

• Ozer A, Bruick RK . Regulation of HIF by prolyl hydroxylases: recruitment of the candidate tumor suppressor protein ING4 . Cell Cycle . 4 . 9 . 1153–6 . September 2005 . 16096374 . 10.4161/cc.4.9.2040 . free .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . September 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM, Huang GY, Chen Z, Chen MD, Chen JL . Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning . Proceedings of the National Academy of Sciences of the United States of America . 97 . 17 . 9543–8 . August 2000 . 10931946 . 16901 . 10.1073/pnas.160270997 . 2000PNAS...97.9543H . free .
• Garkavtsev I, Kozin SV, Chernova O, Xu L, Winkler F, Brown E, Barnett GH, Jain RK . The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis . Nature . 428 . 6980 . 328–32 . March 2004 . 15029197 . 10.1038/nature02329 . 2004Natur.428..328G . 4427531 .
• Zhang X, Xu LS, Wang ZQ, Wang KS, Li N, Cheng ZH, Huang SZ, Wei DZ, Han ZG . ING4 induces G2/M cell cycle arrest and enhances the chemosensitivity to DNA-damage agents in HepG2 cells . FEBS Letters . 570 . 1–3 . 7–12 . July 2004 . 15251430 . 10.1016/j.febslet.2004.06.010 . 12379202 .
• Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Morrin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Research . 14 . 10B . 2121–7 . October 2004 . 15489334 . 528928 . 10.1101/gr.2596504 .
• Kim S, Chin K, Gray JW, Bishop JM . A screen for genes that suppress loss of contact inhibition: identification of ING4 as a candidate tumor suppressor gene in human cancer . Proceedings of the National Academy of Sciences of the United States of America . 101 . 46 . 16251–6 . November 2004 . 15528276 . 528940 . 10.1073/pnas.0407158101 . 2004PNAS..10116251K . free .
• Zhang X, Wang KS, Wang ZQ, Xu LS, Wang QW, Chen F, Wei DZ, Han ZG . Nuclear localization signal of ING4 plays a key role in its binding to p53 . Biochemical and Biophysical Research Communications . 331 . 4 . 1032–8 . June 2005 . 15882981 . 10.1016/j.bbrc.2005.04.023 .
• Ozer A, Wu LC, Bruick RK . The candidate tumor suppressor ING4 represses activation of the hypoxia inducible factor (HIF) . Proceedings of the National Academy of Sciences of the United States of America . 102 . 21 . 7481–6 . May 2005 . 15897452 . 1140452 . 10.1073/pnas.0502716102 . 2005PNAS..102.7481O . free .
• Gunduz M, Nagatsuka H, Demircan K, Gunduz E, Cengiz B, Ouchida M, Tsujigiwa H, Yamachika E, Fukushima K, Beder L, Hirohata S, Ninomiya Y, Nishizaki K, Shimizu K, Nagai N . Frequent deletion and down-regulation of ING4, a candidate tumor suppressor gene at 12p13, in head and neck squamous cell carcinomas . Gene . 356 . 109–17 . August 2005 . 15935570 . 10.1016/j.gene.2005.02.014 .
• Huda Zoghbi . Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y . Substrate and functional diversity of lysine acetylation revealed by a proteomics survey . Molecular Cell . 23 . 4 . 607–18 . August 2006 . 16916647 . 10.1016/j.molcel.2006.06.026 . free .
• Unoki M, Shen JC, Zheng ZM, Harris CC . Novel splice variants of ING4 and their possible roles in the regulation of cell growth and motility . The Journal of Biological Chemistry . 281 . 45 . 34677–86 . November 2006 . 16973615 . 10.1074/jbc.M606296200 . free .
• Raho G, Miranda C, Tamborini E, Pierotti MA, Greco A . Detection of novel mRNA splice variants of human ING4 tumor suppressor gene . Oncogene . 26 . 36 . 5247–57 . August 2007 . 17325660 . 10.1038/sj.onc.1210335 . free .
• Zhang X, Lin DH, Jin Y, Wang KS, Zhang Y, Babilonia E, Wang Z, Wang Z, Giebisch G, Han ZG, Wang WH . Inhibitor of growth 4 (ING4) is up-regulated by a low K intake and suppresses renal outer medullary K channels (ROMK) by MAPK stimulation . Proceedings of the National Academy of Sciences of the United States of America . 104 . 22 . 9517–22 . May 2007 . 17517644 . 1890526 . 10.1073/pnas.0703383104 . 2007PNAS..104.9517Z . free .

Notes and References

1. Shiseki M, Nagashima M, Pedeux RM, Kitahama-Shiseki M, Miura K, Okamura S, Onogi H, Higashimoto Y, Appella E, Yokota J, Harris CC . p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity . Cancer Research . 63 . 10 . 2373–8 . May 2003 . 12750254 .
2. Web site: Entrez Gene: ING4 inhibitor of growth family, member 4.
3. Garkavtsev I, Kozin SV, Chernova O, Xu L, Winkler F, Brown E, Barnett GH, Jain RK . The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis . Nature . 428 . 6980 . 328–32 . March 2004 . 15029197 . 10.1038/nature02329 . 2004Natur.428..328G . 4427531 .
4. Tsai KW, Tseng HC, Lin WC . Two wobble-splicing events affect ING4 protein subnuclear localization and degradation . Experimental Cell Research . 314 . 17 . 3130–41 . October 2008 . 18775696 . 10.1016/j.yexcr.2008.08.002 .