RRC ID 49722
Author Nakade K, Lin CS, Chen XY, Tsai MH, Wuputra K, Zhu ZW, Pan JZ, Yokoyama KK.
Title Jun dimerization protein 2 controls hypoxia-induced replicative senescence via both the p16Ink4a-pRb and Arf-p53 pathways.
Journal FEBS Open Bio
Abstract The main regulators of replicative senescence in mice are p16Ink4a and Arf, inhibitors of cell cycle progression. Jun dimerization protein 2 (JDP2)-deficient mouse embryonic fibroblasts are resistant to replicative senescence through recruitment of the Polycomb repressive complexes 1 and 2 to the promoter of the gene that encodes p16Ink4a and inhibits the methylation of lysine 27 of the histone H3 locus. However, whether or not JDP2 is able to regulate the chromatin signaling of either p16Ink4a-pRb or Arf-p53, or both, in response to oxidative stress remains elusive. Thus, this study sought to clarify this point. We demonstrated that the introduction of JDP2 leads to upregulation of p16Ink4a and Arf and decreases cell proliferation in the presence of environmental (20% O2), but not in low (3% O2) oxygen. JDP2-mediated growth suppression was inhibited by the downregulation of both p16Ink4a and Arf. Conversely, the forced expression of p16Ink4a or Arf inhibited cell growth even in the absence of JDP2. The downregulation of both the p53 and pRb pathways, but not each individually, was sufficient to block JDP2-dependent growth inhibition. These data suggest that JDP2 induces p16Ink4a and Arf by mediating signals from oxidative stress, resulting in cell cycle arrest via both the p16Ink4a-pRb and Arf-p53 pathways.
Volume 7(11)
Pages 1793-1804
Published 2017-11-1
DOI 10.1002/2211-5463.12325
PII FEB412325
PMID 29123987
PMC PMC5666393
IF 2.231
Times Cited 0
DNA material CSII-CMV-MCS (RDB04377) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393).