Inhibition of centriole duplication by centrobin depletion leads to p38-p53 mediated cell-cycle arrest.
Previously, we have identified a novel centrosomal protein centrobin that asymmetrically localizes to the daughter centriole. We found that depletion of centrobin expression inhibited the centriole duplication and impaired cytokinesis. However, the biological significance of centrobin in the cell cycle remains unknown. In the current study, we observed that silencing centrobin significantly inhibited the proliferation of lung cancer cell A549 and prevented the cells from G1 to S transition, whereas the growth rate of lung cancer cell line H1299, a p53-null cell line, was not affected. Furthermore, we demonstrated that the G1-S-phase arrest induced by centrobin knockdown in A549 cells is mediated by the upregulation of cell-cycle regulator p53, which is associated with the activation of cellular stress induced p38 pathway instead of DNA damage induced ATM pathway. Inhibition of p38 activity or downregulation of p38 expression could overcome the cell-cycle arrest caused by centrobin depletion. Taken together, our current findings demonstrated that centrobin plays an important role in the progression of cell cycle, and a tight association between the cell-cycle progression and defective centrosomes caused by depletion of centrobin.
Song
Libing
L
Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China. lb.song1@gmail.com
Dai
Ting
T
Xiong
Huaping
H
Lin
Chuyong
C
Lin
Huanxin
H
Shi
Tingting
T
Li
Jun
J
D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002502:Centrioles / Q000201:enzymology*; D016193:G1 Phase; D055785:Gene Knockdown Techniques; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D016196:S Phase; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
C507203:CNTROB protein, human; D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D048051:p38 Mitogen-Activated Protein Kinases; D001973:Bromodeoxyuridine