The action mechanism of the Myc inhibitor termed Omomyc may give clues on how to target Myc for cancer therapy.

Recent evidence points to Myc--a multifaceted bHLHZip transcription factor deregulated in the majority of human cancers--as a priority target for therapy. How to target Myc is less clear, given its involvement in a variety of key functions in healthy cells. Here we report on the action mechanism of...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mauro Savino, Daniela Annibali, Nicoletta Carucci, Emilia Favuzzi, Michael D Cole, Gerard I Evan, Laura Soucek, Sergio Nasi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/87fb9854901348e2bd4e187527a28c7e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:87fb9854901348e2bd4e187527a28c7e
record_format	dspace
spelling	oai:doaj.org-article:87fb9854901348e2bd4e187527a28c7e2021-11-18T06:49:48ZThe action mechanism of the Myc inhibitor termed Omomyc may give clues on how to target Myc for cancer therapy.1932-620310.1371/journal.pone.0022284https://doaj.org/article/87fb9854901348e2bd4e187527a28c7e2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21811581/?tool=EBIhttps://doaj.org/toc/1932-6203Recent evidence points to Myc--a multifaceted bHLHZip transcription factor deregulated in the majority of human cancers--as a priority target for therapy. How to target Myc is less clear, given its involvement in a variety of key functions in healthy cells. Here we report on the action mechanism of the Myc interfering molecule termed Omomyc, which demonstrated astounding therapeutic efficacy in transgenic mouse cancer models in vivo. Omomyc action is different from the one that can be obtained by gene knockout or RNA interference, approaches designed to block all functions of a gene product. This molecule--instead--appears to cause an edge-specific perturbation that destroys some protein interactions of the Myc node and keeps others intact, with the result of reshaping the Myc transcriptome. Omomyc selectively targets Myc protein interactions: it binds c- and N-Myc, Max and Miz-1, but does not bind Mad or select HLH proteins. Specifically, it prevents Myc binding to promoter E-boxes and transactivation of target genes while retaining Miz-1 dependent binding to promoters and transrepression. This is accompanied by broad epigenetic changes such as decreased acetylation and increased methylation at H3 lysine 9. In the presence of Omomyc, the Myc interactome is channeled to repression and its activity appears to switch from a pro-oncogenic to a tumor suppressive one. Given the extraordinary therapeutic impact of Omomyc in animal models, these data suggest that successfully targeting Myc for cancer therapy might require a similar twofold action, in order to prevent Myc/Max binding to E-boxes and, at the same time, keep repressing genes that would be repressed by Myc.Mauro SavinoDaniela AnnibaliNicoletta CarucciEmilia FavuzziMichael D ColeGerard I EvanLaura SoucekSergio NasiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e22284 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mauro Savino Daniela Annibali Nicoletta Carucci Emilia Favuzzi Michael D Cole Gerard I Evan Laura Soucek Sergio Nasi The action mechanism of the Myc inhibitor termed Omomyc may give clues on how to target Myc for cancer therapy.
description	Recent evidence points to Myc--a multifaceted bHLHZip transcription factor deregulated in the majority of human cancers--as a priority target for therapy. How to target Myc is less clear, given its involvement in a variety of key functions in healthy cells. Here we report on the action mechanism of the Myc interfering molecule termed Omomyc, which demonstrated astounding therapeutic efficacy in transgenic mouse cancer models in vivo. Omomyc action is different from the one that can be obtained by gene knockout or RNA interference, approaches designed to block all functions of a gene product. This molecule--instead--appears to cause an edge-specific perturbation that destroys some protein interactions of the Myc node and keeps others intact, with the result of reshaping the Myc transcriptome. Omomyc selectively targets Myc protein interactions: it binds c- and N-Myc, Max and Miz-1, but does not bind Mad or select HLH proteins. Specifically, it prevents Myc binding to promoter E-boxes and transactivation of target genes while retaining Miz-1 dependent binding to promoters and transrepression. This is accompanied by broad epigenetic changes such as decreased acetylation and increased methylation at H3 lysine 9. In the presence of Omomyc, the Myc interactome is channeled to repression and its activity appears to switch from a pro-oncogenic to a tumor suppressive one. Given the extraordinary therapeutic impact of Omomyc in animal models, these data suggest that successfully targeting Myc for cancer therapy might require a similar twofold action, in order to prevent Myc/Max binding to E-boxes and, at the same time, keep repressing genes that would be repressed by Myc.
format	article
author	Mauro Savino Daniela Annibali Nicoletta Carucci Emilia Favuzzi Michael D Cole Gerard I Evan Laura Soucek Sergio Nasi
author_facet	Mauro Savino Daniela Annibali Nicoletta Carucci Emilia Favuzzi Michael D Cole Gerard I Evan Laura Soucek Sergio Nasi
author_sort	Mauro Savino
title	The action mechanism of the Myc inhibitor termed Omomyc may give clues on how to target Myc for cancer therapy.
title_short	The action mechanism of the Myc inhibitor termed Omomyc may give clues on how to target Myc for cancer therapy.
title_full	The action mechanism of the Myc inhibitor termed Omomyc may give clues on how to target Myc for cancer therapy.
title_fullStr	The action mechanism of the Myc inhibitor termed Omomyc may give clues on how to target Myc for cancer therapy.
title_full_unstemmed	The action mechanism of the Myc inhibitor termed Omomyc may give clues on how to target Myc for cancer therapy.
title_sort	action mechanism of the myc inhibitor termed omomyc may give clues on how to target myc for cancer therapy.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/87fb9854901348e2bd4e187527a28c7e
work_keys_str_mv	AT maurosavino theactionmechanismofthemycinhibitortermedomomycmaygivecluesonhowtotargetmycforcancertherapy AT danielaannibali theactionmechanismofthemycinhibitortermedomomycmaygivecluesonhowtotargetmycforcancertherapy AT nicolettacarucci theactionmechanismofthemycinhibitortermedomomycmaygivecluesonhowtotargetmycforcancertherapy AT emiliafavuzzi theactionmechanismofthemycinhibitortermedomomycmaygivecluesonhowtotargetmycforcancertherapy AT michaeldcole theactionmechanismofthemycinhibitortermedomomycmaygivecluesonhowtotargetmycforcancertherapy AT gerardievan theactionmechanismofthemycinhibitortermedomomycmaygivecluesonhowtotargetmycforcancertherapy AT laurasoucek theactionmechanismofthemycinhibitortermedomomycmaygivecluesonhowtotargetmycforcancertherapy AT sergionasi theactionmechanismofthemycinhibitortermedomomycmaygivecluesonhowtotargetmycforcancertherapy AT maurosavino actionmechanismofthemycinhibitortermedomomycmaygivecluesonhowtotargetmycforcancertherapy AT danielaannibali actionmechanismofthemycinhibitortermedomomycmaygivecluesonhowtotargetmycforcancertherapy AT nicolettacarucci actionmechanismofthemycinhibitortermedomomycmaygivecluesonhowtotargetmycforcancertherapy AT emiliafavuzzi actionmechanismofthemycinhibitortermedomomycmaygivecluesonhowtotargetmycforcancertherapy AT michaeldcole actionmechanismofthemycinhibitortermedomomycmaygivecluesonhowtotargetmycforcancertherapy AT gerardievan actionmechanismofthemycinhibitortermedomomycmaygivecluesonhowtotargetmycforcancertherapy AT laurasoucek actionmechanismofthemycinhibitortermedomomycmaygivecluesonhowtotargetmycforcancertherapy AT sergionasi actionmechanismofthemycinhibitortermedomomycmaygivecluesonhowtotargetmycforcancertherapy
_version_	1718424362961338368

The action mechanism of the Myc inhibitor termed Omomyc may give clues on how to target Myc for cancer therapy.

Ejemplares similares