Cyclin D1 in low-dose radiation-induced adaptive resistance

K. M. Ahmed, M. Fan, D. Nantajit, N. Cao, Jian-Jian Li

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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 14-3-3ζ in unstressed cells and mutation of 14-3-3ζ Ser-58 to Asp (S58D) significantly impaired 14-3-3ζ binding to cyclin D1. The formation of cyclin D1/14-3-3ζ complex was differently regulated by exposure to low (10-cGy X-ray) versus high (5-Gy γ-ray) doses of radiation. Unlike exposure to 5-Gy that predominantly enhanced cyclin D1 nuclear accumulation, LDIR induced the dissociation of the cyclin D1/14-3-3ζ 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 (Δψm) in LDIR-treated cells. Consistently, blocking cyclin D1/Bax formation by cyclin D1 siRNA reversed Δψm 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.

Original languageEnglish (US)
Pages (from-to)6738-6748
Number of pages11
JournalOncogene
Volume27
Issue number53
DOIs
StatePublished - Nov 13 2008
Externally publishedYes

Fingerprint

Cyclin D1
Radiation
Small Interfering RNA
X-Rays
Apoptosis
Mitochondrial Membrane Potential
Cell Cycle Checkpoints
Ionizing Radiation
Keratinocytes
DNA Damage

Keywords

  • 14-3-3
  • Adaptive response
  • Bax
  • Cyclin D1
  • Human keratinocytes
  • Radiation resistance

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Cyclin D1 in low-dose radiation-induced adaptive resistance. / Ahmed, K. M.; Fan, M.; Nantajit, D.; Cao, N.; Li, Jian-Jian.

In: Oncogene, Vol. 27, No. 53, 13.11.2008, p. 6738-6748.

Research output: Contribution to journalArticle

Ahmed, KM, Fan, M, Nantajit, D, Cao, N & Li, J-J 2008, 'Cyclin D1 in low-dose radiation-induced adaptive resistance', Oncogene, vol. 27, no. 53, pp. 6738-6748. https://doi.org/10.1038/onc.2008.265
Ahmed, K. M. ; Fan, M. ; Nantajit, D. ; Cao, N. ; Li, Jian-Jian. / Cyclin D1 in low-dose radiation-induced adaptive resistance. In: Oncogene. 2008 ; Vol. 27, No. 53. pp. 6738-6748.
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