Poly(ADP-ribose) polymerase-1 regulates vimentin expression in lung cancer cells.
Vimentin is one of the mammalian intermediate filament proteins. It is expressed in cells of mesenchymal origin and is characteristic of proliferating cells at the fetal stage. During malignancy, vimentin expression is activated in certain lung epithelial cells. Examination of a group of lung cancer cells showed a marked difference in their vimentin expression. The difference in vimentin expression among lung cancer cells is due to differential regulation at the transcriptional level. Analysis of the vimentin promoter revealed a 102-bp promoter sequence that is important for promoter activity in a lung cancer cell line in which vimentin is strongly expressed. This promoter region interacts with poly(ADP-ribose) polymerase-1 (PARP-1), which is also a transcription regulator. Exogenous expression of PARP-1 increased vimentin promoter activity. A shortened PARP-1 without the COOH-terminal catalytic domain showed the same promoter activation effect. Treatment of cells with H(2)O(2) reduced PARP-1 and vimentin expression at the protein level. H(2)O(2) also dose dependently suppressed vimentin promoter activity in cells overexpressing PARP-1. These results demonstrate that vimentin expression in lung cancer cells is regulated at the transcriptional level and that PARP-1 binds and activates the vimentin promoter independent of its catalytic domain and may play a role in H(2)O(2)-induced inhibition of vimentin expression.
Chu
Shijian
S
McGuire VA Medical Center, Virginia Commonwealth University, Richmond, Virginia 23249, USA. schu@vcu.edu
Xu
Haishan
H
Ferro
Thomas J
TJ
Rivera
Paola X
PX
D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008156:Luciferases; D008168:Lung / Q000502:physiology; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D010449:Peptide Mapping; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D011401:Promoter Regions, Genetic; D020218:Response Elements; D017384:Sequence Deletion; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014746:Vimentin / Q000235:genetics* / Q000378:metabolism
D016877:Oxidants; D014746:Vimentin; D006861:Hydrogen Peroxide; D008156:Luciferases; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases