TY - JOUR

T1 - Clasp2 ensures mitotic fidelity and prevents differentiation of epidermal keratinocytes

AU - Shahbazi, Marta N.

AU - Peña-Jimenez, Daniel

AU - Antonucci, Francesca

AU - Drosten, Matthias

AU - Perez-Moreno, Mirna

N1 - © 2017. Published by The Company of Biologists Ltd.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Differentiation

KW - Cell Line, Transformed

KW - Cells, Cultured

KW - DNA Damage

KW - Epidermis

KW - Gene Knockdown Techniques

KW - Humans

KW - Keratinocytes

KW - Mice, Inbred C57BL

KW - Microtubule-Associated Proteins

KW - Mitosis

KW - Tumor Suppressor Protein p53

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1242/jcs.194787

DO - 10.1242/jcs.194787

M3 - Journal article

C2 - 28069833

VL - 130

SP - 683

EP - 688

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 4

ER -