NFBD1/MDC1 participates in the regulation of G2/M transition in mammalian cells.
NFBD1/MDC1 is a large nuclear protein involved in the early cellular response to DNA damage. Upon DNA damage, NFBD1 has an ability to facilitate the efficient DNA repair. In the present study, we have found that, in addition to DNA damage response, NFBD1 plays a critical role in the regulation of G2/M transition. Expression study using synchronized HeLa cells demonstrated that, like the mitotic kinase Plk1, NFBD1 expression level is maximal in G2/M-phase of the cell cycle. siRNA-mediated knockdown of NFBD1 resulted in G2/M arrest as well as simultaneous apoptosis in association with a significant increase in the amounts of gammaH2AX and pro-apoptotic p73. Since a remarkable down-regulation of mitotic phospho-histone H3 was detectable in NFBD1-knocked down cells, it is likely that knocking down of NFBD1 inhibits G2/M transition. Taken together, our present findings suggest that NFBD1 has a pivotal role in the regulation of proper mitotic entry.
Division of Biochemistry and Anti-tumor Research, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.
Youquan
Y
Bu
Yusuke
Y
Suenaga
Rintaro
R
Okoshi
Meixiang
M
Sang
Natsumi
N
Kubo
Fangzhou
F
Song
Akira
A
Nakagawara
Toshinori
T
Ozaki
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000235:genetics; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D016195:G2 Phase / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C413163:MDC1 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C000606460:TP73 protein, human; D015534:Trans-Activators; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins