title: Clasp2 ensures mitotic fidelity and prevents differentiation of epidermal keratinocytes.
abstract: Epidermal homeostasis is tightly controlled by a balancing act of self-renewal or terminal differentiation of proliferating basal keratinocytes. An increase in DNA content as a consequence of a mitotic block is a recognized mechanism underlying keratinocyte differentiation, but the molecular mechanisms involved in this process are not yet fully understood. Using cultured primary keratinocytes, here we report that the expression of the mammalian microtubule and kinetochore-associated protein Clasp2 is intimately associated with the basal proliferative makeup of keratinocytes, and its deficiency leads to premature differentiation. Clasp2-deficient keratinocytes exhibit increased centrosomal numbers and numerous mitotic alterations, including multipolar spindles and chromosomal misalignments that overall result in mitotic stress and a high DNA content. Such mitotic block prompts premature keratinocyte differentiation in a p53-dependent manner in the absence of cell death. Our findings reveal a new role for Clasp2 in governing keratinocyte undifferentiated features and highlight the presence of surveillance mechanisms that prevent cell cycle entry in cells that have alterations in the DNA content.
authors.affiliation: Epithelial Cell Biology Group, Cancer Cell Biology Programme, Spanish Cancer Research Centre (CNIO), Madrid 28029, Spain.
authors.forename: Marta N
authors.initials: MN
authors.lastname: Shahbazi
authors.affiliation: Epithelial Cell Biology Group, Cancer Cell Biology Programme, Spanish Cancer Research Centre (CNIO), Madrid 28029, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Peña-Jimenez
authors.affiliation: Epithelial Cell Biology Group, Cancer Cell Biology Programme, Spanish Cancer Research Centre (CNIO), Madrid 28029, Spain.
authors.forename: Francesca
authors.initials: F
authors.lastname: Antonucci
authors.affiliation: Experimental Oncology Group, Molecular Oncology Programme, Spanish Cancer Research Centre (CNIO), Madrid 28029, Spain.
authors.forename: Matthias
authors.initials: M
authors.lastname: Drosten
authors.affiliation: Epithelial Cell Biology Group, Cancer Cell Biology Programme, Spanish Cancer Research Centre (CNIO), Madrid 28029, Spain maperez@cnio.es.
authors.forename: Mirna
authors.identifier: 0000-0002-0170-6406
authors.initials: M
authors.lastname: Perez-Moreno
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004249:DNA Damage; D000078404:Epidermal Cells; D055785:Gene Knockdown Techniques; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008938:Mitosis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C497851:CLASP2 protein, human; C506523:CLASP2 protein, mouse; D008869:Microtubule-Associated Proteins; D016159:Tumor Suppressor Protein p53
keywords: Cell cycle; Clasp2; Differentiation; Keratinocytes; Microtubules