biostudies-literatureJacob JTNational Institutes of Healthjcs254094https://www.ebi.ac.uk/biostudies/studies/S-EPMC7648610biostudies-literatureUnknown133(20)Keratin 17 (KRT17; K17), a non-lamin intermediate filament protein, was recently found to occur in the nucleus. We report here on K17-dependent differences in nuclear morphology, chromatin organization, and cell proliferation. Human tumor keratinocyte cell lines lacking K17 exhibit flatter nuclei relative to normal. Re-expression of wild-type K17, but not a mutant form lacking an intact nuclear localization signal (NLS), rescues nuclear morphology in KRT17-null cells. Analyses of primary cultures of skin keratinocytes from a mouse strain expressing K17 with a mutated NLS corroborated these findings. Proteomics screens identified K17-interacting nuclear proteins with known roles in gene expression, chromatin organization and RNA processing. Key histone modifications and LAP2β (an isoform enJournal of cell scienceKeratin 17 regulates nuclear morphology and chromatin organization.PMC7648610AR044232Matunis MJCoulombe PAJacob JTPoll BGNair RRPineda CMHobbs RPfalseKeratin 17 regulates nuclear morphology and chromatin organization.Keratin 17 (KRT17; K17), a non-lamin intermediate filament protein, was recently found to occur in the nucleus. We report here on K17-dependent differences in nuclear morphology, chromatin organization, and cell proliferation. Human tumor keratinocyte cell lines lacking K17 exhibit flatter nuclei relative to normal. Re-expression of wild-type K17, but not a mutant form lacking an intact nuclear localization signal (NLS), rescues nuclear morphology in KRT17-null cells. Analyses of primary cultures of skin keratinocytes from a mouse strain expressing K17 with a mutated NLS corroborated these findings. Proteomics screens identified K17-interacting nuclear proteins with known roles in gene expression, chromatin organization and RNA processing. Key histone modifications and LAP2β (an isoform en2020-01-01T00:00:00Z2020 Oct2025-04-20T03:43:39.969Z2025-04-20T03:43:39.969ZS-EPMC76486103300884510.1242/jcs.254094