Manipulating Myc for Reparative Regeneration

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2024 Apr 5

PMID 38577503

Authors

Camilla Ascanelli

Rowda Dahir

Catherine H Wilson

Affiliations

Soon will be listed here.

Abstract

The Myc family of proto-oncogenes is a key node for the signal transduction of external pro-proliferative signals to the cellular processes required for development, tissue homoeostasis maintenance, and regeneration across evolution. The tight regulation of Myc synthesis and activity is essential for restricting its oncogenic potential. In this review, we highlight the central role that Myc plays in regeneration across the animal kingdom (from Cnidaria to echinoderms to Chordata) and how Myc could be employed to unlock the regenerative potential of non-regenerative tissues in humans for therapeutic purposes. Mastering the fine balance of harnessing the ability of Myc to promote transcription without triggering oncogenesis may open the door to many exciting opportunities for therapeutic development across a wide array of diseases.

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References

Delmore J, Issa G, Lemieux M, Rahl P, Shi J, Jacobs H . BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011; 146(6):904-17. PMC: 3187920. DOI: 10.1016/j.cell.2011.08.017. View

Zindy F, Eischen C, Randle D, Kamijo T, Cleveland J, Sherr C . Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization. Genes Dev. 1998; 12(15):2424-33. PMC: 317045. DOI: 10.1101/gad.12.15.2424. View

Jonas J, Laybutt D, Steil G, Trivedi N, Pertusa J, Van de Casteele M . High glucose stimulates early response gene c-Myc expression in rat pancreatic beta cells. J Biol Chem. 2001; 276(38):35375-81. DOI: 10.1074/jbc.M105020200. View

Grandori C, Cowley S, James L, Eisenman R . The Myc/Max/Mad network and the transcriptional control of cell behavior. Annu Rev Cell Dev Biol. 2000; 16:653-99. DOI: 10.1146/annurev.cellbio.16.1.653. View

Couture J, Collazo E, Trievel R . Molecular recognition of histone H3 by the WD40 protein WDR5. Nat Struct Mol Biol. 2006; 13(8):698-703. DOI: 10.1038/nsmb1116. View

Boikova A, Bywater M, Quaife-Ryan G, Straube J, Thompson L, Ascanelli C . HRas and Myc synergistically induce cell cycle progression and apoptosis of murine cardiomyocytes. Front Cardiovasc Med. 2022; 9:948281. PMC: 9630352. DOI: 10.3389/fcvm.2022.948281. View

Araki R, Hoki Y, Uda M, Nakamura M, Jincho Y, Tamura C . Crucial role of c-Myc in the generation of induced pluripotent stem cells. Stem Cells. 2011; 29(9):1362-70. DOI: 10.1002/stem.685. View

Shi Y, Shu B, Yang R, Xu Y, Xing B, Liu J . Wnt and Notch signaling pathway involved in wound healing by targeting c-Myc and Hes1 separately. Stem Cell Res Ther. 2015; 6:120. PMC: 4501079. DOI: 10.1186/s13287-015-0103-4. View

Amati B, Dalton S, Brooks M, Littlewood T, Evan G, Land H . Transcriptional activation by the human c-Myc oncoprotein in yeast requires interaction with Max. Nature. 1992; 359(6394):423-6. DOI: 10.1038/359423a0. View

10.

Cheung L, Zervou S, Mattsson G, Abouna S, Zhou L, Ifandi V . c-Myc directly induces both impaired insulin secretion and loss of β-cell mass, independently of hyperglycemia in vivo. Islets. 2010; 2(1):37-45. DOI: 10.4161/isl.2.1.10196. View

11.

Hishida T, Vazquez-Ferrer E, Hishida-Nozaki Y, Takemoto Y, Hatanaka F, Yoshida K . Myc Supports Self-Renewal of Basal Cells in the Esophageal Epithelium. Front Cell Dev Biol. 2022; 10:786031. PMC: 8931341. DOI: 10.3389/fcell.2022.786031. View

12.

Wang H, Mannava S, Grachtchouk V, Zhuang D, Soengas M, Gudkov A . c-Myc depletion inhibits proliferation of human tumor cells at various stages of the cell cycle. Oncogene. 2007; 27(13):1905-15. PMC: 3144565. DOI: 10.1038/sj.onc.1210823. View

13.

Senyo S, Steinhauser M, Pizzimenti C, Yang V, Cai L, Wang M . Mammalian heart renewal by pre-existing cardiomyocytes. Nature. 2012; 493(7432):433-6. PMC: 3548046. DOI: 10.1038/nature11682. View

14.

Liu L, OuYang M, Rao J, Zou T, Xiao L, Chung H . Competition between RNA-binding proteins CELF1 and HuR modulates MYC translation and intestinal epithelium renewal. Mol Biol Cell. 2015; 26(10):1797-810. PMC: 4436827. DOI: 10.1091/mbc.E14-11-1500. View

15.

Liu J, Levens D . Making myc. Curr Top Microbiol Immunol. 2006; 302:1-32. DOI: 10.1007/3-540-32952-8_1. View

16.

Audic Y, Hartley R . Post-transcriptional regulation in cancer. Biol Cell. 2004; 96(7):479-98. DOI: 10.1016/j.biolcel.2004.05.002. View

17.

Quaife-Ryan G, Sim C, Ziemann M, Kaspi A, Rafehi H, Ramialison M . Multicellular Transcriptional Analysis of Mammalian Heart Regeneration. Circulation. 2017; 136(12):1123-1139. PMC: 5598916. DOI: 10.1161/CIRCULATIONAHA.117.028252. View

18.

Baena E, Gandarillas A, Vallespinos M, Zanet J, Bachs O, Redondo C . c-Myc regulates cell size and ploidy but is not essential for postnatal proliferation in liver. Proc Natl Acad Sci U S A. 2005; 102(20):7286-91. PMC: 1129100. DOI: 10.1073/pnas.0409260102. View

19.

Han Y, Zhong C, Hong L, Wang Y, Qiao L, Qiu J . Effect of c-myc on the ultrastructural structure of cochleae in guinea pigs with noise induced hearing loss. Biochem Biophys Res Commun. 2009; 390(3):458-62. DOI: 10.1016/j.bbrc.2009.09.091. View

20.

Magadum A, Kurian A, Chepurko E, Sassi Y, Hajjar R, Zangi L . Specific Modified mRNA Translation System. Circulation. 2020; 142(25):2485-2488. PMC: 7768930. DOI: 10.1161/CIRCULATIONAHA.120.047211. View