UVB-Induced G2 Arrest of Human Melanocytes Involves Cdc2 Sequestration by Gadd45a in Nuclear Speckles

Exposure to solar UVB radiation is involved in the development of cutaneous melanoma. We previously showed that human melanocytes and melanoma cells respond to UVB radiation via a p53-independent pathway involving GADD45A activation. Here, we determined that UVB-induction of Gadd45a is necessary for...

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Veröffentlicht in:Cell cycle (Georgetown, Tex.) Tex.), 2006-08, Vol.5 (16), p.1859-1864
Hauptverfasser: Fayolle, Caroline, Pourchet, Julie, Cohen, Aurélie, Pedeux, Rémy, Puisieux, Alain, Fromentel, Claude Caron de, Dore, Jean-François, Voeltzel, Thibault
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container_end_page 1864
container_issue 16
container_start_page 1859
container_title Cell cycle (Georgetown, Tex.)
container_volume 5
creator Fayolle, Caroline
Pourchet, Julie
Cohen, Aurélie
Pedeux, Rémy
Puisieux, Alain
Fromentel, Claude Caron de
Dore, Jean-François
Voeltzel, Thibault
description Exposure to solar UVB radiation is involved in the development of cutaneous melanoma. We previously showed that human melanocytes and melanoma cells respond to UVB radiation via a p53-independent pathway involving GADD45A activation. Here, we determined that UVB-induction of Gadd45a is necessary for G2 arrest and that Gadd45a and its partner p21Waf1 co-localize in nuclear bodies called Nuclear Speckles. We further observed that UVB-induced G2 arrest is associated with Cdc2 accumulation in these Nuclear Speckles. Knock-down of Gadd45a expression by RNA interference prevents both UVB-induced Cdc2 accumulation in Nuclear Speckles and G2 arrest. Our results demonstrate that UVB-induced G2 arrest of melanoma cells is Gadd45a-dependent. Furthermore, we show that Cdc2 sequestration by Gadd45a occurs in Nuclear Speckles, suggesting a new role for these nuclear bodies, so far only linked to RNA maturation.
doi_str_mv 10.4161/cc.5.16.3119
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subjects Binding
Biology
Bioscience
Calcium
Cancer
CDC2 Protein Kinase
CDC2 Protein Kinase - metabolism
Cell
Cell Cycle
Cell Cycle Proteins
Cell Cycle Proteins - metabolism
Cell Line, Tumor
Cell Nucleus
Cell Nucleus - enzymology
Cell Proliferation
Cycle
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinase Inhibitor p21 - metabolism
G2 Phase
Humans
Landes
Life Sciences
Melanocytes
Melanocytes - enzymology
Melanocytes - radiation effects
Nuclear Proteins
Nuclear Proteins - metabolism
Organogenesis
Proteins
Ultraviolet Rays
title UVB-Induced G2 Arrest of Human Melanocytes Involves Cdc2 Sequestration by Gadd45a in Nuclear Speckles
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