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 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.
Fayolle
Caroline
C
INSERM U590, Oncogenèse et Progression Tumorale, Université Lyon1, Centre Léon Bérard, Lyon, France.
Pourchet
Julie
J
Cohen
Aurélie
A
Pedeux
Rémy
R
Puisieux
Alain
A
Caron de Fromentel
Claude
C
Dorè
Jean-François
JF
Voeltzel
Thibault
T
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
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