Plk1-dependent phosphorylation regulates functions of DNA topoisomerase IIalpha in cell cycle progression.
J Biol Chem
; 283(10): 6209-21, 2008 Mar 07.
Article
en En
| MEDLINE
| ID: mdl-18171681
ABSTRACT
Plk1 (Polo-like kinase 1) has been documented as a critical regulator of many mitotic events. However, increasing evidence supports the notion that Plk1 might also have functions outside of mitosis. Using biochemical fractionation and RNA interference approaches, we found that Plk1 was required for both G(1)/S and G(2)/M phases and that DNA topoisomerase IIalpha (topoIIalpha) was a potential target for Plk1 in both interphase and mitosis. Plk1 phosphorylates Ser(1337) and Ser(1524) of topoIIalpha. Overexpression of an unphosphorylatable topoIIalpha mutant led to S phase arrest, suggesting that Plk1-associated phosphorylation first occurs in S phase. Moreover, overexpression of the unphosphorylatable topoIIalpha mutant activated the ATM/R-dependent DNA damage checkpoint, probably due to reduced catalytic activity of topoIIalpha, and resulted in accumulation of catenated DNA. Finally, we showed that wild type topoIIalpha, but not the unphosphorylatable mutant, was able to rescue topoIIalpha depletion-induced defects in sister chromatid segregation, indicating that Plk1-associated phosphorylation is essential for the functions of topoIIalpha in mitosis.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Ciclo Celular
/
Cromátides
/
Proteínas Proto-Oncogénicas
/
Proteínas Serina-Treonina Quinasas
/
ADN-Topoisomerasas de Tipo II
/
Proteínas de Ciclo Celular
/
ADN Encadenado
/
Proteínas de Unión al ADN
/
Antígenos de Neoplasias
Límite:
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos