title: UVB-induced G2 arrest of human melanocytes involves Cdc2 sequestration by Gadd45a in nuclear speckles.
abstract: 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 G(2) arrest and that Gadd45a and its partner p21(Waf1) colocalize in nuclear bodies called Nuclear Speckles. We further observed that UVB-induced G(2) 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 G(2) arrest. Our results demonstrate that UVB-induced G(2) 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.
authors.affiliation: INSERM U590, Oncogenèse et Progression Tumorale, Université Lyon1, Centre Léon Bérard, Lyon, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Fayolle
authors.forename: Julie
authors.initials: J
authors.lastname: Pourchet
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cohen
authors.forename: Rémy
authors.initials: R
authors.lastname: Pedeux
authors.forename: Alain
authors.initials: A
authors.lastname: Puisieux
authors.forename: Claude
authors.initials: C
authors.lastname: Caron de Fromentel
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dorè
authors.forename: Thibault
authors.initials: T
authors.lastname: Voeltzel
mesh_terms: D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000201:enzymology*; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D016195:G2 Phase; D006801:Humans; D008544:Melanocytes / Q000201:enzymology / Q000528:radiation effects*; D009687:Nuclear Proteins / Q000378:metabolism*; D014466:Ultraviolet Rays; D000097642:GADD45 Proteins
chemical_list: D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009687:Nuclear Proteins; C493956:CDKN1A protein, human; C439070:GADD45A protein, human; D000097642:GADD45 Proteins