Phorbol-12-myristate-13-acetate-induced protein 1 explained

Phorbol-12-myristate-13-acetate-induced protein 1 is a protein that in humans is encoded by the PMAIP1 gene, and is also known as Noxa.^{[1] [2] [3]}

Noxa (Latin for damage) is a pro-apoptotic member of the Bcl-2 protein family.^[4] Bcl-2 family members can form hetero- or homodimers, and they act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The expression of Noxa is regulated by the tumor suppressor p53, and Noxa has been shown to be involved in p53-mediated apoptosis.

Interactions

Noxa has been shown to interact with:

• BCL2-like 1,^[5]
• Bcl-2,^[5] and
• MCL1.^{[6] [7] [8]}

See also

• Apoptosis
• Apoptosome
• Bcl-2
• Bcl-2-associated X protein (BAX)
• BH3 interacting domain death agonist (BID)
• Caspases
• Cytochrome c
• Mitochondrion
• p53 upregulated modulator of apoptosis (PUMA)
• 12-O-Tetradecanoylphorbol-13-acetate (Phorbol-12-myristate-13-acetate)

Further reading

• 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 . 288 . 5468 . 1053–8 . 2000 . 10807576 . 10.1126/science.288.5468.1053 . 2000Sci...288.1053O .
• Seo YW, Shin JN, Ko KH, Cha JH, Park JY, Lee BR, Yun CW, Kim YM, Seol DW, Kim DW, Yin XM, Kim TH . The molecular mechanism of Noxa-induced mitochondrial dysfunction in p53-mediated cell death. . J. Biol. Chem. . 278 . 48 . 48292–9 . 2004 . 14500711 . 10.1074/jbc.M308785200 . free .
• Kim JY, Ahn HJ, Ryu JH, Suk K, Park JH . BH3-only protein Noxa is a mediator of hypoxic cell death induced by hypoxia-inducible factor 1alpha. . J. Exp. Med. . 199 . 1 . 113–24 . 2004 . 14699081 . 1887730 . 10.1084/jem.20030613 .
• Yakovlev AG, Di Giovanni S, Wang G, Liu W, Stoica B, Faden AI . BOK and NOXA are essential mediators of p53-dependent apoptosis. . J. Biol. Chem. . 279 . 27 . 28367–74 . 2004 . 15102863 . 10.1074/jbc.M313526200 . free .
• Qin JZ, Stennett L, Bacon P, Bodner B, Hendrix MJ, Seftor RE, Seftor EA, Margaryan NV, Pollock PM, Curtis A, Trent JM, Bennett F, Miele L, Nickoloff BJ . p53-independent NOXA induction overcomes apoptotic resistance of malignant melanomas. . Mol. Cancer Ther. . 3 . 8 . 895–902 . 2005 . 10.1158/1535-7163.895.3.8 . 15299072 . 34940117 . free .
• Flinterman M, Guelen L, Ezzati-Nik S, Killick R, Melino G, Tominaga K, Mymryk JS, Gäken J, Tavassoli M . E1A activates transcription of p73 and Noxa to induce apoptosis. . J. Biol. Chem. . 280 . 7 . 5945–59 . 2005 . 15572378 . 10.1074/jbc.M406661200 . free .
• Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC . Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. . Mol. Cell . 17 . 3 . 393–403 . 2005 . 15694340 . 10.1016/j.molcel.2004.12.030 . free .
• Sun Y, Leaman DW . Involvement of Noxa in cellular apoptotic responses to interferon, double-stranded RNA, and virus infection. . J. Biol. Chem. . 280 . 16 . 15561–8 . 2005 . 15705586 . 10.1074/jbc.M412630200 . free.
• Ceballos E, Muñoz-Alonso MJ, Berwanger B, Acosta JC, Hernández R, Krause M, Hartmann O, Eilers M, León J . Inhibitory effect of c-Myc on p53-induced apoptosis in leukemia cells. Microarray analysis reveals defective induction of p53 target genes and upregulation of chaperone genes. . Oncogene . 24 . 28 . 4559–71 . 2005 . 15856024 . 10.1038/sj.onc.1208652 . 21190604 .
• Willis SN, Chen L, Dewson G, Wei A, Naik E, Fletcher JI, Adams JM, Huang DC . Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. . Genes Dev. . 19 . 11 . 1294–305 . 2005 . 15901672 . 1142553 . 10.1101/gad.1304105 .
• Alves NL, Derks IA, Berk E, Spijker R, van Lier RA, Eldering E . The Noxa/Mcl-1 axis regulates susceptibility to apoptosis under glucose limitation in dividing T cells. . Immunity . 24 . 6 . 703–16 . 2006 . 16782027 . 10.1016/j.immuni.2006.03.018 . free .
• Obexer P, Geiger K, Ambros PF, Meister B, Ausserlechner MJ . FKHRL1-mediated expression of Noxa and Bim induces apoptosis via the mitochondria in neuroblastoma cells. . Cell Death Differ. . 14 . 3 . 534–47 . 2007 . 16888645 . 10.1038/sj.cdd.4402017 . free .
• Fribley AM, Evenchik B, Zeng Q, Park BK, Guan JY, Zhang H, Hale TJ, Soengas MS, Kaufman RJ, Wang CY . Proteasome inhibitor PS-341 induces apoptosis in cisplatin-resistant squamous cell carcinoma cells by induction of Noxa. . J. Biol. Chem. . 281 . 42 . 31440–7 . 2006 . 16928686 . 10.1074/jbc.M604356200 . free.
• Smit LA, Hallaert DY, Spijker R, de Goeij B, Jaspers A, Kater AP, van Oers MH, van Noesel CJ, Eldering E . Differential Noxa/Mcl-1 balance in peripheral versus lymph node chronic lymphocytic leukemia cells correlates with survival capacity. . Blood . 109 . 4 . 1660–8 . 2007 . 17038534 . 10.1182/blood-2006-05-021683 . 16995479 .
• Armstrong JL, Veal GJ, Redfern CP, Lovat PE . Role of Noxa in p53-independent fenretinide-induced apoptosis of neuroectodermal tumours. . Apoptosis . 12 . 3 . 613–22 . 2007 . 17216584 . 10.1007/s10495-006-0020-1 . 41674871 .
• Doffo J, Bamopoulos SA, Köse H, Orben F, Zang C, Pons M, et al. . NOXA expression drives synthetic lethality to RUNX1 inhibition in pancreatic cancer. . Proc Natl Acad Sci USA . 119 . 9 . 2022 . 35197278 . 8892327. 10.1073/pnas.2105691119 . free . 2022PNAS..11905691D .

Notes and References

1. Hijikata M, Kato N, Sato T, Kagami Y, Shimotohno K . Molecular cloning and characterization of a cDNA for a novel phorbol-12-myristate-13-acetate-responsive gene that is highly expressed in an adult T-cell leukemia cell line . J Virol . 64 . 10 . 4632–9 . October 1990 . 2398525 . 247947 . 10.1128/JVI.64.10.4632-4639.1990.
2. Jansson AK, Emterling AM, Arbman G, Sun XF . Noxa in colorectal cancer: a study on DNA, mRNA and protein expression . Oncogene . 22 . 30 . 4675–8 . July 2003 . 12879012 . 10.1038/sj.onc.1206655 .
3. Web site: Entrez Gene: PMAIP1 phorbol-12-myristate-13-acetate-induced protein 1.
4. 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 . 288 . 5468 . 1053–1058 . May 2000 . 10807576 . 10.1126/science.288.5468.1053 . 2000Sci...288.1053O .
5. 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 . 288 . 5468 . 1053–8 . May 2000 . 10807576 . 10.1126/science.288.5468.1053. 2000Sci...288.1053O .
6. Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC . Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function . Mol. Cell . 17 . 3 . 393–403 . February 2005 . 15694340 . 10.1016/j.molcel.2004.12.030 . free .
7. Willis SN, Chen L, Dewson G, Wei A, Naik E, Fletcher JI, Adams JM, Huang DC . Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins . Genes Dev. . 19 . 11 . 1294–305 . June 2005 . 15901672 . 1142553 . 10.1101/gad.1304105 .
8. Heckmeier . Philipp J. . Ruf . Jeannette . Janković . Brankica G. . Hamm . Peter . MCL-1 promiscuity and the structural resilience of its binding partners . The Journal of Chemical Physics . 7 March 2023 . 158 . 9 . 10.1063/5.0137239. 36889945 . 2023JChPh.158i5101H . free . 2211.08934 .