Clasp2 ensures mitotic fidelity and prevents differentiation of epidermal keratinocytes
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Clasp2 ensures mitotic fidelity and prevents differentiation of epidermal keratinocytes. / Shahbazi, Marta N.; Peña-Jimenez, Daniel; Antonucci, Francesca; Drosten, Matthias; Perez-Moreno, Mirna.
I: Journal of Cell Science, Bind 130, Nr. 4, 2017, s. 683-688.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 -
ID: 188368196