Clasp2 ensures mitotic fidelity and prevents differentiation of epidermal keratinocytes
Authors
Marta N. Shahbazi, Daniel Peña-Jimenez, Francesca Antonucci, Matthias Drosten and Mirna Perez-Moreno
Institution
Epithelial Cell Biology Group, Cancer Cell Biology Programme, Spanish Cancer Research Centre (CNIO)
Country
Spain
Year
2017
Journal
Journal of Cell Science
Abstract
Epidermal homeostasis is tightly controlled by a balancing act of selfrenewal
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 kinetochoreassociated
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.