{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:45:17Z","timestamp":1772160317443,"version":"3.50.1"},"reference-count":74,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,9,24]],"date-time":"2022-09-24T00:00:00Z","timestamp":1663977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:p>The healing of wounded skin is a highly organized process involving a massive cell in\u2010 and outflux, proliferation and tissue remodelling. It is well accepted that metabolic constraints such as diabetes mellitus, overweight or anorexia impairs wound healing. Indeed, wound inflammation involves a boost of overall metabolic changes. As wound healing converges inflammatory processes that are also common to transformation, we investigate the functional role of the pro\u2010neoplastic factor pyruvate kinase (PK) M2 and its metabolic active splice variant PKM1 in keratinocytes. Particularly, we challenge the impact of reciprocal ablation of PKM1 or two expression. Here, CRISPR\/Cas9 genome editing of the PKM gene in HaCaT reveals an unexpected mutational bias at the 3'SS of exon 9, whereas no preference for any particular kind of mutation at exon 10 3' splice, despite the close vicinity (400 nucleotides apart) and sequence similarity between the two sites. Furthermore, as opposed to transient silencing of PKM2, exclusion splicing of PKM2 via genome editing mutually increases PKM1 mRNA and protein expression and compensates for the absence of PKM2, whereas the reciprocal elimination of PKM1 splicing reduces PKM2 expression and impedes cell proliferation, thus unveiling an essential role for PKM1 in growth and metabolic balance of HaCaT keratinocytes.<\/jats:p>","DOI":"10.1111\/febs.16625","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T17:19:14Z","timestamp":1662743954000},"page":"2338-2365","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Reciprocal abrogation of\n                    <scp>PKM<\/scp>\n                    isoforms: contradictory outcomes and differing impact of splicing signal on\n                    <scp>CRISPR<\/scp>\n                    \/Cas9 mediates gene editing in keratinocytes"],"prefix":"10.1111","volume":"290","author":[{"given":"Simon P.","family":"Nold","sequence":"first","affiliation":[{"name":"Pharmazentrum Frankfurt\/ZAFES, General Pharmacology and Toxicology, Faculty of Medicine Goethe University Frankfurt  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khrystyna","family":"Sych","sequence":"additional","affiliation":[{"name":"Pharmazentrum Frankfurt\/ZAFES, General Pharmacology and Toxicology, Faculty of Medicine Goethe University Frankfurt  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gergely","family":"Imre","sequence":"additional","affiliation":[{"name":"Pharmazentrum Frankfurt\/ZAFES, General Pharmacology and Toxicology, Faculty of Medicine Goethe University Frankfurt  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominik C.","family":"Fuhrmann","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Biochemistry I Goethe 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