Induction of cereblon by NF-E2-related factor 2 in neuroblastoma cells exposed to hypoxia-reoxygenation.
Cereblon is a protein encoded by the CRBN gene, which has been associated with human autosomal recessive nonsyndromic mental retardation. However, little is known about the regulation of CRBN expression. Following exposure of mouse neuroblastoma N2A cells to hypoxia/reoxygenation (H/R), mRNA and protein expression of CRBN were increased. To better understand how CRBN expression is regulated, the promoter region of the mouse CRBN gene was characterized functionally. Deletion mutations and site-directed mutagenesis led to the identification of a functional NF-E2-related factor 2 (Nrf2)-binding site. Electrophoretic mobility shift analysis indicated that Nrf2 binds to a putative binding site in the CRBN promoter. Nrf2 overexpression and tert-butylhydroquinone treatment enhanced CRBN protein expression. These results imply that Nrf2 stimulates CRBN gene transcription under H/R conditions in neuronal cells.
Lee
Kyung Jin
KJ
School of Life Sciences and Cell Dynamics Research Center, Gwangju Institute Science and Technology (GIST), Gwangju 500-712, Republic of Korea.
Lee
Kwang Min
KM
Jo
Sooyeon
S
Kang
Keon Wook
KW
Park
Chul-Seung
CS
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D017353:Gene Deletion; D006873:Hydroquinones / Q000494:pharmacology; D008607:Intellectual Disability / Q000235:genetics; D051379:Mice; D016297:Mutagenesis, Site-Directed; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020218:Response Elements
D048868:Adaptor Proteins, Signal Transducing; C549921:Crbn protein, mouse; D006873:Hydroquinones; D051267:NF-E2-Related Factor 2; D009419:Nerve Tissue Proteins; C018855:2-tert-butylhydroquinone; D010100:Oxygen