Abstract
The tumour suppressor gene p53 is extensively studied for its importance in cancer. In its active conformation, p53 is tetrameric and one domain – the tetramerization domain – permits the oligomerization of this protein. Until recently, little attention was given to this domain because, in contrast to the DNA-binding domain, it is not often mutated in cancer. However, various experimental studies have shown evidence that the tetramerization domain is essential for DNA binding, protein–protein interactions, post-translational modifications, and p53 degradation. Moreover, single mutations in the tetramerization domain can inactivate the wild-type protein in a manner similar to that seen with mutations in the DNA-binding domain. Interestingly, the phenotype of several tetramerization domain mutants differs from that observed with DNA-binding domain mutants. In this review, current knowledge about the importance of the tetramerization domain to the function of p53 will be summarized.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Appella E, Anderson CW . 2000 Pathol. Biol. (Paris) 48: 227–245
Atz J, Wagner P, Roemer K . 2000 J. Cell. Biochem. 76: 572–584
Balagurumoorthy P, Sakamoto H, Lewis MS, Zambrano N, Clore GM, Gronenborn AM, Appella E, Harrington RE . 1995 Proc. Natl. Acad. Sci. USA 92: 8591–8595
Bargonetti J, Manfredi JJ, Chen X, Marshak DR, Prives C . 1993 Genes Dev. 7: 2565–2574
Bates S, Vousden KH . 1999 Cell. Mol. Life Sci. 55: 28–37
Blagosklonny MV . 2000 Faseb. J. 14: 1901–1907
Brachmann RK, Vidal M, Boeke JD . 1996 Proc. Natl. Acad. Sci. USA 93: 4091–4095
Chen J, Marechal V, Levine AJ . 1993 Mol. Cell. Biol. 13: 4107–4114
Chène P . 1998 J. Mol. Biol. 281: 205–209
Chène P . 1999 J. Mol. Biol. 288: 883–890
Chène P . 2000 Biotechniques 28: 240–242
Chène P, Bechter E . 1999a J. Mol. Biol. 288: 891–897
Chène P, Bechter E . 1999b J. Mol. Biol. 286: 1269–1274
Chène P, Mittl P, Grutter M . 1997 J. Mol. Biol. 273: 873–881
Cho Y, Gorina S, Jeffrey PD, Pavletich NP . 1994 Science 265: 346–355
Chou PY, Fasman GD . 1974 Biochemistry 13: 211–222
Clore GM, Ernst J, Clubb R, Omichinski JG, Kennedy WM, Sakaguchi K, Appella E, Gronenborn AM . 1995a Nat. Struct. Biol. 2: 321–333
Clore GM, Omichinski JG, Sakaguchi K, Zambrano N, Sakamoto H, Appella E, Gronenborn AM . 1994 Science 265: 386–391
Clore GM, Omichinski JG, Sakaguchi K, Zambrano N, Sakamoto H, Appella E, Gronenborn AM . 1995b Science 267: 1515–1516
Davison TS, Vagner C, Kaghad M, Ayed A, Caput D, Arrowsmith CH . 1999 J. Biol. Chem. 274: 18709–18714
Davison TS, Yin P, Nie E, Kay C, Arrowsmith CH . 1998 Oncogene 17: 651–656
Delphin C, Huang KP, Scotto C, Chapel A, Vincon M, Chambaz E, Garin J, Baudier J . 1997 Eur. J. Biochem. 245: 684–692
Di Como CJ, Gaiddon C, Prives C . 1999 Mol. Cell. Biol. 19: 1438–1449
Dobner T, Horikoshi N, Rubenwolf S, Shenk T . 1996 Science 272: 1470–1473
Eliyahu D, Goldfinger N, Pinhasi-Kimhi O, Shaulsky G, Skurnik Y, Arai N, Rotter V, Oren M . 1988 Oncogene 3: 313–321
Frazier MW, He X, Wang J, Gu Z, Cleveland JL, Zambetti GP . 1998 Mol. Cell. Biol. 18: 3735–3743
Friedman PN, Chen X, Bargonetti J, Prives C . 1993 Proc. Natl. Acad. Sci. USA 90: 3319–3323
Gannon JV, Greaves R, Iggo R, Lane DP . 1990 EMBO J. 9: 1595–1602
Gotz C, Scholtes P, Prowald A, Schuster N, Nastainczyk W, Montenarh M . 1999 Mol. Cell. Biochem. 191: 111–120
Hainaut P, Hollstein M . 2000 Adv. Cancer Res. 77: 81–137
Hainaut P, Milner J . 1993 Cancer Res. 53: 4469–4473
Halazonetis TD, Davis LJ, Kandil AN . 1993 EMBO J. 12: 1021–1028
Halazonetis TD, Kandil AN . 1993 EMBO J. 12: 5057–5064
Halevy O, Hall A, Oren M . 1989 Mol. Cell. Biol. 9: 3385–3392
Hixon ML, Flores A, Wagner M, Gualberto A . 2000 Histol. Histopathol. 15: 551–556
Hollstein M, Hergenhahn M, Yang Q, Bartsch H, Wang ZQ, Hainaut P . 1999 Mutat. Res. 431: 199–209
Hollstein M, Sidransky D, Vogelstein B, Harris CC . 1991 Science 253: 49–53
Hupp TR, Meek DW, Midgley CA, Lane DP . 1992 Cell 71: 875–886
Ikeda A, Sun X, Li Y, Zhang Y, Eckner R, Doi TS, Takahashi T, Obata Y, Yoshioka K, Yamamoto K . 2000 Biochem. Biophys. Res. Commun. 272: 375–379
Ishioka C, Shimodaira H, Englert C, Shimada A, Osada M, Jia LQ, Suzuki T, Gamo M, Kanamaru R . 1997 Biochem. Biophys. Res. Commun. 232: 54–60
Iwabuchi K, Li B, Bartel P, Fields S . 1993 Oncogene 8: 1693–1696
Jeffrey PD, Gorina S, Pavletich NP . 1995 Science 267: 1498–1502
Johnson CR, Morin PE, Arrowsmith CH, Freire E . 1995 Biochemistry 34: 5309–5316
Ko LJ, Prives C . 1996 Genes Dev. 10: 1054–1072
Kraiss S, Quaiser A, Oren M, Montenarh M . 1988 J. Virol. 62: 4737–4744
Kubbutat MH, Ludwig RL, Ashcroft M, Vousden KH . 1998 Mol. Cell. Biol. 18: 5690–5698
Lanyi A, Deb D, Seymour RC, Ludes-Meyers JH, Subler MA, Deb S . 1998 Oncogene 16: 3169–3176
Lee W, Harvey TS, Yin Y, Yau P, Litchfield D, Arrowsmith CH . 1994 Nat. Struct. Biol. 1: 877–890
Levine AJ . 1997 Cell 88: 323–331
Levine AJ, Wu MC, Chang A, Silver A, Attiyeh EF, Lin J, Epstein CB . 1995 Ann. N. Y. Acad. Sci. 768: 111–128
Lin Y, Nomura T, Yamashita T, Dorjsuren D, Tang H, Murakami S . 1997 Cancer Res. 57: 5137–5142
Liu X, Miller CW, Koeffler PH, Berk AJ . 1993 Mol. Cell. Biol. 13: 3291–3300
Lomax ME, Barnes DM, Gilchrist R, Picksley SM, Varley JM, Camplejohn RS . 1997 Oncogene 14: 1869–1874
Lomax ME, Barnes DM, Hupp TR, Picksley SM, Camplejohn RS . 1998 Oncogene 17: 643–649
Maki CG . 1999 J. Biol. Chem. 274: 16531–16535
Malanga M, Pleschke JM, Kleczkowska HE, Althaus FR . 1998 J. Biol. Chem. 273: 11839–11843
Marin MC, Jost CA, Brooks LA, Irwin MS, O'Nions J, Tidy JA, James N, McGregor JM, Harwood CA, Yulug IG, Vousden KH, Allday MJ, Gusterson B, Ikawa S, Hinds PW, Crook T, Kaelin Jr WG . 2000 Nat. Genet. 25: 47–54
Marston NJ, Jenkins JR, Vousden KH . 1995 Oncogene 10: 1709–1715
Massimi P, Pim D, Bertoli C, Bouvard V, Banks L . 1999 Oncogene 18: 7748–7754
Mateu MG, Fersht AR . 1998 EMBO J. 17: 2748–2758
Mateu MG, Fersht AR . 1999 Proc. Natl. Acad. Sci. USA 96: 3595–3599
Mateu MG, Sanchez Del Pino MM, Fersht AR . 1999 Nat. Struct. Biol. 6: 191–198
McCormick F, Clark R, Harlow E, Tjian R . 1981 Nature 292: 63–65
McCoy M, Stavridi ES, Waterman JL, Wieczorek AM, Opella SJ, Halazonetis TD . 1997 EMBO J. 16: 6230–6236
McLure KG, Lee PW . 1996 Oncogene 13: 1297–1303
McLure KG, Lee PW . 1998 EMBO J. 17: 3342–3350
McLure KG, Lee PW . 1999 EMBO J. 18: 763–770
Meek DW . 1999 Oncogene 18: 7666–7675
Michalovitz D, Halevy O, Oren M . 1990 Cell 62: 671–680
Miller M, Lubkowski J, Rao JK, Danishefsky AT, Omichinski JG, Sakaguchi K, Sakamoto H, Appella E, Gronenborn AM, Clore GM . 1996 FEBS Lett. 399: 166–170
Milner J, Medcalf EA . 1990 J. Mol. Biol. 216: 481–484
Milner J, Medcalf EA . 1991 Cell 65: 765–774
Mittl PR, Chène P, Grutter MG . 1998 Acta Crystallogr. D. Biol. Crystallogr. 54: 86–89
Nagaich AK, Zhurkin VB, Durell SR, Jernigan RL, Appella E, Harrington RE . 1999 Proc. Natl. Acad. Sci. USA 96: 1875–1880
Nie Y, Li HH, Bula CM, Liu X . 2000 Mol. Cell. Biol. 20: 741–748
Oren M, Rotter V . 1999 Cell. Mol. Life Sci. 55: 9–11
Pavletich NP, Chambers KA, Pabo CO . 1993 Genes Dev. 7: 2556–2564
Roemer K . 1999 Biol. Chem. 380: 879–887
Rollenhagen C, Chène P . 1998 Int. J. Cancer 78: 372–376
Sakaguchi K, Sakamoto H, Lewis MS, Anderson CW, Erickson JW, Appella E, Xie D . 1997 Biochemistry 36: 10117–10124
Sakamoto H, Lewis MS, Kodama H, Appella E, Sakaguchi K . 1994 Proc. Natl. Acad. Sci. USA 91: 8974–8978
Sang BC, Chen JY, Minna J, Barbosa MS . 1994 Oncogene 9: 853–859
Schmieg FI, Simmons DT . 1988 Virology 164: 132–140
Selivanova G, Wiman KG . 1995 Adv. Cancer Res. 66: 143–180
Shaulian E, Zauberman A, Milner J, Davies EA, Oren M . 1993 EMBO J. 12: 2789–2797
Shieh SY, Ahn J, Tamai K, Taya Y, Prives C . 2000 Genes Dev. 14: 289–300
Soussi T, Caron de Fromentel C, May P . 1990 Oncogene 5: 945–952
Soussi T, Dehouche K, Beroud C . 2000 Hum. Mutat. 15: 105–113
Stavridi ES, Chehab NH, Caruso LC, Halazonetis TD . 1999 Protein Sci. 8: 1773–1779
Steele RJ, Thompson AM, Hall PA, Lane DP . 1998 Br. J. Surg. 85: 1460–1467
Stenger JE, Mayr GA, Mann K, Tegtmeyer P . 1992 Mol. Carcinog. 5: 102–106
Stenger JE, Tegtmeyer P, Mayr GA, Reed M, Wang Y, Wang P, Hough PV, Mastrangelo IA . 1994 EMBO J. 13: 6011–6120
Stommel JM, Marchenko ND, Jimenez GS, Moll UM, Hope TJ, Wahl GM . 1999 EMBO J. 18: 1660–1672
Strano S, Munarriz E, Rossi M, Cristofanelli B, Shaul Y, Castagnoli L, Levine AJ, Sacchi A, Cesareni G, Oren M, Blandino G . 2000 J. Biol. Chem. 275: 29503–29512
Sturzbecher HW, Brain R, Addison C, Rudge K, Remm M, Grimaldi M, Keenan E, Jenkins JR . 1992 Oncogene 7: 1513–1523
Subler MA, Martin DW, Deb S . 1994 Oncogene 9: 1351–1359
Surridge C . 1994 Nature 372: 482
Tarunina M, Jenkins JR . 1993 Oncogene 8: 3165–3173
van Oijen MG, Slootweg PJ . 2000 Clin. Cancer Res. 6: 2138–2145
Varley JM, McGown G, Thorncroft M, Cochrane S, Morrison P, Woll P, Kelsey AM, Mitchell EL, Boyle J, Birch JM, Evans DG . 1996 Oncogene 12: 2437–2442
Wang Y, Farmer G, Soussi T, Prives C . 1995a Oncogene 10: 779–784
Wang Y, Reed M, Wang P, Stenger JE, Mayr G, Anderson ME, Schwedes JF, Tegtmeyer P . 1993 Genes Dev. 7: 2575–2586
Wang Y, Schwedes JF, Parks D, Mann K, Tegtmeyer P . 1995b Mol. Cell. Biol. 15: 2157–2165
Waterman JL, Shenk JL, Halazonetis TD . 1995 EMBO J. 14: 512–519
Zhang W, Guo XY, Deisseroth AB . 1994 Oncogene 9: 2513–2121
Acknowledgements
I would like to thank Dr S Ferrari for his critical reading of the manuscript.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chène, P. The role of tetramerization in p53 function. Oncogene 20, 2611–2617 (2001). https://doi.org/10.1038/sj.onc.1204373
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1204373
Keywords
This article is cited by
-
Emerging role and therapeutic implications of p53 in intervertebral disc degeneration
Cell Death Discovery (2023)
-
TP53-mutated acute myeloid leukemia and myelodysplastic syndrome: biology, treatment challenges, and upcoming approaches
Annals of Hematology (2023)
-
A super-potent tetramerized ACE2 protein displays enhanced neutralization of SARS-CoV-2 virus infection
Scientific Reports (2021)
-
TP53 isoform junction reads based analysis in malignant and normal contexts
Scientific Reports (2021)
-
Predicting Peptide Oligomeric State Through Chemical Artificial Intelligence
International Journal of Peptide Research and Therapeutics (2021)