Open AccessCyclin D1 in low-dose radiation-induced adaptive resistance
Author(s) -
Kazi Mokim Ahmed,
Ming Fan,
Danupon Nantajit,
Ning Cao,
Jian Jian Li
Publication year - 2008
Publication title -
oncogene
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 3.395
H-Index - 342
eISSN - 1476-5594
pISSN - 0950-9232
DOI - 10.1038/onc.2008.265
Subject(s) - cyclin d1 , biology , cyclin d , cyclin b , cyclin , cyclin a , cancer research , cyclin a2 , dna damage , microbiology and biotechnology , cell cycle , cell cycle checkpoint , apoptosis , genetics , dna
Cyclin D1 is involved in cell-cycle arrest in DNA-damage response. This study tested the hypothesis that cyclin D1 regulates mitochondrial apoptosis. Cyclin D1 was induced by low-dose ionizing radiation (LDIR; 10-cGy X-ray) in human keratinocytes with an adaptive radioresistance that can be inhibited by short interfering RNA (siRNA)-mediated cyclin D1 inhibition. Cyclin D1 was found to form complex with chaperon 14-3-3zeta in unstressed cells and mutation of 14-3-3zeta Ser-58 to Asp (S58D) significantly impaired 14-3-3zeta binding to cyclin D1. The formation of cyclin D1/14-3-3zeta complex was differently regulated by exposure to low (10-cGy X-ray) versus high (5-Gy gamma-ray) doses of radiation. Unlike exposure to 5-Gy that predominantly enhanced cyclin D1 nuclear accumulation, LDIR induced the dissociation of the cyclin D1/14-3-3zeta complex without nuclear translocation, indicating that cytosolic accumulation of cyclin D1 was required for LDIR-induced adaptive response. Further studies revealed a direct interaction of cyclin D1 with proapoptotic Bax and an improved mitochondrial membrane potential (Deltapsi(m)) in LDIR-treated cells. Consistently, blocking cyclin D1/Bax formation by cyclin D1 siRNA reversed Deltapsi(m) and inhibited the LDIR-associated antiapoptotic response. These results demonstrate the evidence that cytosolic cyclin D1 is able to regulate apoptosis by interaction with Bax in LDIR-induced adaptive resistance.