TP53 Regulates Transcription of Cell Death Genes

Kruiswijk F, Labuschagne CF, Vousden KH. p53 in survival, death and metabolic health: a lifeguard with a licence to kill. Nature Reviews Molecular Cell Biology. 2015 Jun 23;16(7):393–405. doi: 10.1038/nrm4007.; Bieging KT, Mello SS, Attardi LD. Unravelling mechanisms of p53-mediated tumour suppression. Nat Rev Cancer. 2014 May;14(5):359–70. PMID: 24739573; PMCID: PMC4049238.; Celardo I, Grespi F, Antonov A, Bernassola F, Garabadgiu AV, Melino G, Amelio I. Caspase-1 is a novel target of p63 in tumor suppression. Cell Death & Disease. 2013 May 23;4(5):e645. doi: 10.1038/cddis.2013.175.; Wilson AM, Morquette B, Abdouh M, Unsain N, Barker PA, Feinstein E, Bernier G, Di Polo A. ASPP1/2 Regulate p53-Dependent Death of Retinal Ganglion Cells through PUMA and Fas/CD95 ActivationIn Vivo. J. Neurosci. 2013 Jan 30;33(5):2205–16. doi: 10.1523/jneurosci.2635-12.2013.; Giam M, Okamoto T, Mintern JD, Strasser A, Bouillet P. Bcl-2 family member Bcl-G is not a proapoptotic protein. Cell Death & Disease. 2012 Oct 11;3(10):e404. doi: 10.1038/cddis.2012.130.; Wang L, Xing H, Tian Z, Peng L, Li Y, Tang K, Rao Q, Wang M, Wang J. iASPPsv antagonizes apoptosis induced by chemotherapeutic agents in MCF-7 cells and mouse thymocytes. Biochemical and Biophysical Research Communications. 2012 Aug;424(3):414–20. doi: 10.1016/j.bbrc.2012.06.124.; Ingermann AR, Yang Y, Han J, Mikami A, Garza AE, Mohanraj L, Fan L, Idowu M, Ware JL, Kim H, Lee D, Oh Y. Identification of a Novel Cell Death Receptor Mediating IGFBP-3-induced Anti-tumor Effects in Breast and Prostate Cancer. Journal of Biological Chemistry. 2010 Sep;285(39):30233–46. doi: 10.1074/jbc.m110.122226.; Schilling T, Schleithoff ES, Kairat A, Melino G, Stremmel W, Oren M, Krammer PH, Müller M. Active transcription of the human FAS/CD95/TNFRSF6 gene involves the p53 family. Biochemical and Biophysical Research Communications. 2009 Sep;387(2):399–404. doi: 10.1016/j.bbrc.2009.07.063.; Saito M, Novak U, Piovan E, Basso K, Sumazin P, Schneider C, Crespo M, Shen Q, Bhagat G, Califano A, Chadburn A, Pasqualucci L, Dalla-Favera R. BCL6 suppression of BCL2 via Miz1 and its disruption in diffuse large B cell lymphoma. Proc Natl Acad Sci U S A. 2009 Jul 07;106(27):11294–9. PMID: 19549844; PMCID: PMC2708681.; Davies L, Gray D, Spiller D, White MRH, Damato B, Grierson I, Paraoan L. P53 apoptosis mediator PERP: localization, function and caspase activation in uveal melanoma. J Cellular Molecular Medi. 2008 Nov 18;13(8b):1995–2007. doi: 10.1111/j.1582-4934.2008.00590.x.; Murray-Zmijewski F, Slee EA, Lu X. A complex barcode underlies the heterogeneous response of p53 to stress. Nature Reviews Molecular Cell Biology. 2008 Sep;9(9):702–12. doi: 10.1038/nrm2451.; Patel S, George R, Autore F, Fraternali F, Ladbury JE, Nikolova PV. Molecular interactions of ASPP1 and ASPP2 with the p53 protein family and the apoptotic promoters PUMA and Bax. Nucleic Acids Res. 2008 Sep;36(16):5139–51. PMID: 18676979; PMCID: PMC2532732.; Riley T, Sontag E, Chen P, Levine A. Transcriptional control of human p53-regulated genes. Nature Reviews Molecular Cell Biology. 2008 May;9(5):402–12. doi: 10.1038/nrm2395.; Zhang A, Rao JN, Zou T, Liu L, Marasa BS, Xiao L, Chen J, Turner DJ, Wang J. p53-Dependent NDRG1 expression induces inhibition of intestinal epithelial cell proliferation but not apoptosis after polyamine depletion. American Journal of Physiology-Cell Physiology. 2007 Jul;293(1):C379–89. doi: 10.1152/ajpcell.00547.2006.; Taira N, Nihira K, Yamaguchi T, Miki Y, Yoshida K. DYRK2 is targeted to the nucleus and controls p53 via Ser46 phosphorylation in the apoptotic response to DNA damage. Mol Cell. 2007 Mar 09;25(5):725–38. doi: 10.1016/j.molcel.2007.02.007. PMID: 17349958.; Brough D, Rothwell NJ. Caspase-1-dependent processing of pro-interleukin-1beta is cytosolic and precedes cell death. J Cell Sci. 2007 Mar 01;120(Pt 5):772–81. doi: 10.1242/jcs.03377. PMID: 17284521.; Margalit O, Amram H, Amariglio N, Simon AJ, Shaklai S, Granot G, Minsky N, Shimoni A, Harmelin A, Givol D, Shohat M, Oren M, Rechavi G. BCL6 is regulated by p53 through a response element frequently disrupted in B-cell non-Hodgkin lymphoma. Blood. 2006 Feb 15;107(4):1599–607. doi: 10.1182/blood-2005-04-1629. PMID: 16249378.; Jain N, Gupta S, Sudhakar Ch, Radha V, Swarup G. Role of p73 in regulating human caspase-1 gene transcription induced by interferon-{gamma} and cisplatin. J Biol Chem. 2005 Nov 04;280(44):36664–73. doi: 10.1074/jbc.m413261200. PMID: 16135520.; Liu X, Yue P, Khuri FR, Sun SY. Decoy receptor 2 (DcR2) is a p53 target gene and regulates chemosensitivity. Cancer Res. 2005 Oct 15;65(20):9169–75. doi: 10.1158/0008-5472.can-05-0939. PMID: 16230375.; Jen KY, Cheung VG. Identification of novel p53 target genes in ionizing radiation response. Cancer Res. 2005 Sep 01;65(17):7666–73. doi: 10.1158/0008-5472.can-05-1039. PMID: 16140933.; Ihrie RA, Marques MR, Nguyen BT, Horner JS, Papazoglu C, Bronson RT, Mills AA, Attardi LD. Perp is a p63-regulated gene essential for epithelial integrity. Cell. 2005 Mar 25;120(6):843–56. doi: 10.1016/j.cell.2005.01.008. PMID: 15797384.; Park WR, Nakamura Y. p53CSV, a novel p53-inducible gene involved in the p53-dependent cell-survival pathway. Cancer Res. 2005 Feb 15;65(4):1197–206. doi: 10.1158/0008-5472.can-04-3339. PMID: 15735003.; Sadasivam S, Gupta S, Radha V, Batta K, Kundu TK, Swarup G. Caspase-1 activator Ipaf is a p53-inducible gene involved in apoptosis. Oncogene. 2005 Jan 20;24(4):627–36. doi: 10.1038/sj.onc.1208201. PMID: 15580302.; Phan RT, Dalla-Favera R. The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells. Nature. 2004 Dec 02;432(7017):635–9. doi: 10.1038/nature03147. PMID: 15577913.; Fei P, Wang W, Kim SH, Wang S, Burns TF, Sax JK, Buzzai M, Dicker DT, McKenna WG, Bernhard EJ, El-Deiry WS. Bnip3L is induced by p53 under hypoxia, and its knockdown promotes tumor growth. Cancer Cell. 2004 Dec;6(6):597–609. doi: 10.1016/j.ccr.2004.10.012. PMID: 15607964.; Stein S, Thomas EK, Herzog B, Westfall MD, Rocheleau JV, Jackson RS, Wang M, Liang P. NDRG1 Is Necessary for p53-dependent Apoptosis. Journal of Biological Chemistry. 2004 Nov;279(47):48930–40. doi: 10.1074/jbc.m400386200.; Liu X, Yue P, Khuri FR, Sun SY. p53 upregulates death receptor 4 expression through an intronic p53 binding site. Cancer Res. 2004 Aug 01;64(15):5078–83. doi: 10.1158/0008-5472.can-04-1195. PMID: 15289308.; Wu M, Xu LG, Su T, Tian Y, Zhai Z, Shu HB. AMID is a p53-inducible gene downregulated in tumors. Oncogene. 2004 Sep 02;23(40):6815–9. doi: 10.1038/sj.onc.1207909. PMID: 15273740.; Li CQ, Robles AI, Hanigan CL, Hofseth LJ, Trudel LJ, Harris CC, Wogan GN. Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 01;64(9):3022–9. doi: 10.1158/0008-5472.can-03-1880. PMID: 15126337.; Ruiz de Almodóvar C, Ruiz-Ruiz C, Rodríguez A, Ortiz-Ferrón G, Redondo JM, López-Rivas A. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) decoy receptor TRAIL-R3 is up-regulated by p53 in breast tumor cells through a mechanism involving an intronic p53-binding site. J Biol Chem. 2004 Feb 06;279(6):4093–101. doi: 10.1074/jbc.m311243200. PMID: 14623878.; Bergamaschi D, Samuels Y, Jin B, Duraisingham S, Crook T, Lu X. ASPP1 and ASPP2: Common Activators of p53 Family Members. Molecular and Cellular Biology. 2004 Feb 01;24(3):1341–50. doi: 10.1128/mcb.24.3.1341-1350.2004.; Ihrie RA, Reczek E, Horner JS, Khachatrian L, Sage J, Jacks T, Attardi LD. Perp is a mediator of p53-dependent apoptosis in diverse cell types. Curr Biol. 2003 Nov 11;13(22):1985–90. doi: 10.1016/j.cub.2003.10.055. PMID: 14614825.; Rikhof B, Corn PG, El-Deiry WS. Caspase 10 Levels are Increased Following DNA Damage in a p53-Dependent Manner. cbt. 2003 Nov 01;2(6):705–10. doi: 10.4161/cbt.2.6.626.; Tomasini R, Samir AA, Carrier A, Isnardon D, Cecchinelli B, Soddu S, Malissen B, Dagorn J, Iovanna JL, Dusetti NJ. TP53INP1s and Homeodomain-interacting Protein Kinase-2 (HIPK2) Are Partners in Regulating p53 Activity. Journal of Biological Chemistry. 2003 Sep;278(39):37722–9. doi: 10.1074/jbc.m301979200.; Passer BJ, Nancy-Portebois V, Amzallag N, Prieur S, Cans C, Roborel de Climens A, Fiucci G, Bouvard V, Tuynder M, Susini L, Morchoisne S, Crible V, Lespagnol A, Dausset J, Oren M, Amson R, Telerman A. The p53-inducible TSAP6 gene product regulates apoptosis and the cell cycle and interacts with Nix and the Myt1 kinase. Proc. Natl. Acad. Sci. U.S.A. 2003 Feb 26;100(5):2284–9. doi: 10.1073/pnas.0530298100.; Sax JK, Fei P, Murphy ME, Bernhard E, Korsmeyer SJ, El-Deiry WS. BID regulation by p53 contributes to chemosensitivity. Nat Cell Biol. 2002 Nov;4(11):842–9. doi: 10.1038/ncb866. PMID: 12402042.; MacLachlan TK, El-Deiry WS. Apoptotic threshold is lowered by p53 transactivation of caspase-6. Proc Natl Acad Sci U S A. 2002 Jul 09;99(14):9492–7. PMID: 12089322; PMCID: PMC123168.; Contente A, Dittmer A, Koch MC, Roth J, Dobbelstein M. A polymorphic microsatellite that mediates induction of PIG3 by p53. Nat Genet. 2002 Mar;30(3):315–20. doi: 10.1038/ng836. PMID: 11919562.; Samuels-Lev Y, O'Connor DJ, Bergamaschi D, Trigiante G, Hsieh JK, Zhong S, Campargue I, Naumovski L, Crook T, Lu X. ASPP proteins specifically stimulate the apoptotic function of p53. Mol Cell. 2001 Oct;8(4):781–94. doi: 10.1016/s1097-2765(01)00367-7. PMID: 11684014.; Robles AI, Bemmels NA, Foraker AB, Harris CC. APAF-1 is a transcriptional target of p53 in DNA damage-induced apoptosis. Cancer Res. 2001 Sep 15;61(18):6660–4. PMID: 11559530.; Okamura S, Arakawa H, Tanaka T, Nakanishi H, Ng CC, Taya Y, Monden M, Nakamura Y. p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis. Mol Cell. 2001 Jul;8(1):85–94. doi: 10.1016/s1097-2765(01)00284-2. PMID: 11511362.; Guan B, Yue P, Clayman GL, Sun SY. Evidence that the death receptor DR4 is a DNA damage-inducible, p53-regulated gene. J Cell Physiol. 2001 Jul;188(1):98–105. doi: 10.1002/jcp.1101. PMID: 11382926.; Gupta S, Radha V, Furukawa Y, Swarup G. Direct Transcriptional Activation of Human Caspase-1 by Tumor Suppressor p53. Journal of Biological Chemistry. 2001 Apr;276(14):10585–8. doi: 10.1074/jbc.c100025200.; Nakano K, Vousden KH. PUMA, a novel proapoptotic gene, is induced by p53. Mol Cell. 2001 Mar;7(3):683–94. doi: 10.1016/s1097-2765(01)00214-3. PMID: 11463392.; Guo B, Godzik A, Reed JC. Bcl-G, a Novel Pro-apoptotic Member of the Bcl-2 Family. Journal of Biological Chemistry. 2001 Jan;276(4):2780–5. doi: 10.1074/jbc.m005889200.; Lin Y, Ma W, Benchimol S. Pidd, a new death-domain-containing protein, is induced by p53 and promotes apoptosis. Nat Genet. 2000 Sep;26(1):122–7. doi: 10.1038/79102. PMID: 10973264.; Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N. Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science. 2000 May 12;288(5468):1053–8. doi: 10.1126/science.288.5468.1053. PMID: 10807576.; Takimoto R, El-Deiry WS. Wild-type p53 transactivates the KILLER/DR5 gene through an intronic sequence-specific DNA-binding site. Oncogene. 2000 Mar 30;19(14):1735–43. doi: 10.1038/sj.onc.1203489. PMID: 10777207.; Attardi LD, Reczek EE, Cosmas C, Demicco EG, McCurrach ME, Lowe SW, Jacks T. PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family. Genes Dev. 2000 Mar 15;14(6):704–18. PMID: 10733530; PMCID: PMC316461.; Wu GS, Burns TF, McDonald ER, Jiang W, Meng R, Krantz ID, Kao G, Gan DD, Zhou JY, Muschel R, Hamilton SR, Spinner NB, Markowitz S, Wu G, el-Deiry WS. KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene. Nat Genet. 1997 Oct;17(2):141–3. doi: 10.1038/ng1097-141. PMID: 9326928.; Buckbinder L, Talbott R, Velasco-Miguel S, Takenaka I, Faha B, Seizinger BR, Kley N. Induction of the growth inhibitor IGF-binding protein 3 by p53. Nature. 1995 Oct 19;377(6550):646–9. doi: 10.1038/377646a0. PMID: 7566179.; Miyashita T, Reed JC. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell. 1995 Jan 27;80(2):293–9. doi: 10.1016/0092-8674(95)90412-3. PMID: 7834749.

Metabolites



Enzyme

EC Number name full name note
2.5.1.60 protein geranylgeranyltransferase type II geranylgeranyl-diphosphate:protein-cysteine geranyltransferase


Proteins

Protein ID name full name
P20133 BET2 Geranylgeranyl transferase type-2 subunit beta
Q00618 BET4 Geranylgeranyl transferase type-2 subunit alpha