eprintid: 1429841 rev_number: 43 eprint_status: archive userid: 608 dir: disk0/01/42/98/41 datestamp: 2014-05-14 18:39:00 lastmod: 2021-10-18 00:05:49 status_changed: 2016-04-05 12:28:21 type: article metadata_visibility: show item_issues_count: 0 creators_name: Yun, MH creators_name: Gates, PB creators_name: Brockes, JP title: Sustained ERK activation underlies reprogramming in regeneration-competent salamander cells and distinguishes them from their mammalian counterparts ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 divisions: G03 keywords: Animals, Cell Cycle, Cell Differentiation, Cell Line, Extracellular Signal-Regulated MAP Kinases, Mammals, Mitogen-Activated Protein Kinases, Muscle Fibers, Skeletal, Regeneration, Urodela note: © 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). abstract: In regeneration-competent vertebrates, such as salamanders, regeneration depends on the ability of various differentiated adult cell types to undergo natural reprogramming. This ability is rarely observed in regeneration-incompetent species such as mammals, providing an explanation for their poor regenerative potential. To date, little is known about the molecular mechanisms mediating natural reprogramming during regeneration. Here, we have identified the extent of extracellular signal-regulated kinase (ERK) activation as a key component of such mechanisms. We show that sustained ERK activation following serum induction is required for re-entry into the cell cycle of postmitotic salamander muscle cells, partially by promoting the downregulation of p53 activity. Moreover, ERK activation induces epigenetic modifications and downregulation of muscle-specific genes such as Sox6. Remarkably, while long-term ERK activation is found in salamander myotubes, only transient activation is seen in their mammalian counterparts, suggesting that the extent of ERK activation could underlie differences in regenerative competence between species. date: 2014-07-08 official_url: http://dx.doi.org/10.1016/j.stemcr.2014.05.009 vfaculties: VFLS oa_status: green full_text_type: pub primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_source: PubMed elements_id: 946905 doi: 10.1016/j.stemcr.2014.05.009 pii: S2213-6711(14)00150-7 lyricists_name: Brockes, Jeremy lyricists_name: Gates, Phillip lyricists_name: Yun, Maximina lyricists_id: JPBRO93 lyricists_id: PGATE52 lyricists_id: MYUNX04 full_text_status: public publication: Stem Cell Reports volume: 3 number: 1 pagerange: 15-23 event_location: United States issn: 2213-6711 citation: Yun, MH; Gates, PB; Brockes, JP; (2014) Sustained ERK activation underlies reprogramming in regeneration-competent salamander cells and distinguishes them from their mammalian counterparts. Stem Cell Reports , 3 (1) pp. 15-23. 10.1016/j.stemcr.2014.05.009 <https://doi.org/10.1016/j.stemcr.2014.05.009>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1429841/1/PIIS2213671114001507.pdf