Cdc25C interacts with PCNA at G2/M transition

Abstract

Cdc25 activates maturation promoting factor (MPF) and promotes mitosis by removing the inhibitory phosphate from the Tyr-15 of Cdc2 in human cells. In this study, we searched the interacting protein(s) of human Cdc25C using the yeast two-hybrid screen and identi®ed proliferating cell nuclear antigen (PCNA) as an interacting partner of Cdc25C. The interaction between Cdc25C and PCNA was con®rmed in vitro and in vivo. Coimmunoprecipitation analyses using human T cell line, Jurkat, further revealed that Cdc25C interacted with PCNA transiently when cells began to enter mitosis. Immuno¯uorescence analysis also showed that Cdc25C and PCNA were transiently co-localized in the nucleus at the beginning of M phase. Together with the previous observations of the interaction between various cdc/ cyclin and PCNA, our ®ndings strongly suggested a potential role of PCNA at the G2 to M phase transition of cell cycle.

Identification of radiation-specific responses from gene expression profile

“…This gross retardation in cell growth after g-irradiation might be due to cell cycle arrest and/or cell death induced by DNA damage (Figure 1b,c). Jurkat T cells were stuck in the G2/M phase even at 2 Gy IR, which might be mediated by Cdc25C and PCNA (Kawabe et al, 2002). In addition, IR-exposed cells showed increased apoptotic fractions upon g-irradiation (Vigorito et al, 1999).…”

DNA damage checkpoint control in cells exposed to ionizing radiation

“…The latter protein binds P21, CDC25C and CDC2-cyclin B, but not simultaneously, and may act as a platform for protein interactions (Xiong et al, 1992;Harper et al, 1993;Kawabe et al, 2002). It appears that binding of P21 and CDC25C to the PCNA-CDC2-cyclin B complex is mutually exclusive ; as a result, P21 interaction with PCNA-CDC2-cyclin B will exclude CDC25C from interacting with CDC2 to dephosphorylate it for mitotic progression.…”

Interference between p53 and cdc25C in cell cycle regulation

“…This complex formation seems to be involved in the regulation of the onset of mitosis. Cdc25C and PCNA were shown to be transiently co-localized in the nucleus at the beginning of M-phase (13). Similar to p53, it is possible that the cdc25C/PCNA interaction might be a mechanism to prevent the premature onset of mitosis.…”

“…Binding of cdc25C to the 14-3-3 protein leads to a nuclear exclusion of cdc25C and thus to inactivation of cdc25C. In a yeast two-hybrid screen PCNA (proliferating cell nuclear antigen) was found as an interaction partner of cdc25C, this interaction was confirmed to appear in vitro and in vivo (13). To date, nothing is known about the functional relevance of this interaction.…”