PRIMA-1 reactivates mutant p53 by covalent binding to the core domain - PubMed
- ️Thu Jan 01 2009
. 2009 May 5;15(5):376-88.
doi: 10.1016/j.ccr.2009.03.003.
Affiliations
- PMID: 19411067
- DOI: 10.1016/j.ccr.2009.03.003
Free article
PRIMA-1 reactivates mutant p53 by covalent binding to the core domain
Jeremy M R Lambert et al. Cancer Cell. 2009.
Free article
Abstract
Restoration of wild-type p53 expression triggers cell death and eliminates tumors in vivo. The identification of mutant p53-reactivating small molecules such as PRIMA-1 opens possibilities for the development of more efficient anticancer drugs. Although the biological effects of PRIMA-1 are well demonstrated, little is known about its molecular mechanism of action. We show here that PRIMA-1 is converted to compounds that form adducts with thiols in mutant p53. Covalent modification of mutant p53 per se is sufficient to induce apoptosis in tumor cells. These findings might facilitate the design of more potent and specific mutant p53-targeting anticancer drugs.
Similar articles
-
PRIMA-1 inhibits growth of breast cancer cells by re-activating mutant p53 protein.
Liang Y, Besch-Williford C, Hyder SM. Liang Y, et al. Int J Oncol. 2009 Nov;35(5):1015-23. doi: 10.3892/ijo_00000416. Int J Oncol. 2009. PMID: 19787255
-
Benakanakere I, Besch-Williford C, Ellersieck MR, Hyder SM. Benakanakere I, et al. Endocr Relat Cancer. 2009 Mar;16(1):85-98. doi: 10.1677/ERC-08-0069. Epub 2008 Dec 15. Endocr Relat Cancer. 2009. PMID: 19075036
-
Izetti P, Hautefeuille A, Abujamra AL, de Farias CB, Giacomazzi J, Alemar B, Lenz G, Roesler R, Schwartsmann G, Osvaldt AB, Hainaut P, Ashton-Prolla P. Izetti P, et al. Invest New Drugs. 2014 Oct;32(5):783-94. doi: 10.1007/s10637-014-0090-9. Epub 2014 May 20. Invest New Drugs. 2014. PMID: 24838627
-
Pharmacological reactivation of mutant p53: from protein structure to the cancer patient.
Wiman KG. Wiman KG. Oncogene. 2010 Jul 29;29(30):4245-52. doi: 10.1038/onc.2010.188. Epub 2010 May 24. Oncogene. 2010. PMID: 20498645 Review.
-
Menichini P, Monti P, Speciale A, Cutrona G, Matis S, Fais F, Taiana E, Neri A, Bomben R, Gentile M, Gattei V, Ferrarini M, Morabito F, Fronza G. Menichini P, et al. Cells. 2021 Jan 7;10(1):98. doi: 10.3390/cells10010098. Cells. 2021. PMID: 33430525 Free PMC article. Review.
Cited by
-
Key Players in the Mutant p53 Team: Small Molecules, Gene Editing, Immunotherapy.
Chasov V, Mirgayazova R, Zmievskaya E, Khadiullina R, Valiullina A, Stephenson Clarke J, Rizvanov A, Baud MGJ, Bulatov E. Chasov V, et al. Front Oncol. 2020 Aug 18;10:1460. doi: 10.3389/fonc.2020.01460. eCollection 2020. Front Oncol. 2020. PMID: 32974171 Free PMC article. Review.
-
Shetzer Y, Molchadsky A, Rotter V. Shetzer Y, et al. Cold Spring Harb Perspect Med. 2016 Oct 3;6(10):a026203. doi: 10.1101/cshperspect.a026203. Cold Spring Harb Perspect Med. 2016. PMID: 27235476 Free PMC article. Review.
-
Full-length p53 tetramer bound to DNA and its quaternary dynamics.
Demir Ö, Ieong PU, Amaro RE. Demir Ö, et al. Oncogene. 2017 Mar 9;36(10):1451-1460. doi: 10.1038/onc.2016.321. Epub 2016 Sep 19. Oncogene. 2017. PMID: 27641333 Free PMC article.
-
PTC596-Induced BMI-1 Inhibition Fights Neuroblastoma Multidrug Resistance by Inducing Ferroptosis.
Valenti GE, Roveri A, Venerando R, Menichini P, Monti P, Tasso B, Traverso N, Domenicotti C, Marengo B. Valenti GE, et al. Antioxidants (Basel). 2023 Dec 19;13(1):3. doi: 10.3390/antiox13010003. Antioxidants (Basel). 2023. PMID: 38275623 Free PMC article.
-
Computational identification of a transiently open L1/S3 pocket for reactivation of mutant p53.
Wassman CD, Baronio R, Demir Ö, Wallentine BD, Chen CK, Hall LV, Salehi F, Lin DW, Chung BP, Hatfield GW, Richard Chamberlin A, Luecke H, Lathrop RH, Kaiser P, Amaro RE. Wassman CD, et al. Nat Commun. 2013;4:1407. doi: 10.1038/ncomms2361. Nat Commun. 2013. PMID: 23360998 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous