Preferential repression of the H subunit of ferritin by adenovirus E1A in NIH-3T3 mouse fibroblasts.
Ferritin is the major intracellular iron-storage protein in eucaryotic cells and plays a prominent role in maintaining intracellular iron homeostasis. We observed that transfection of NIH-3T3 mouse fibroblasts with the adenovirus E1A oncogene specifically repressed the mRNA for one of the subunits of ferritin, ferritin H. This occurred in the absence of any effect of E1A on the mRNA for the L subunit of ferritin. The repression of ferritin H was not a general feature of oncogene expression since transfection of NIH-3T3 cells with H-ras did not affect ferritin composition. Deletion of the conserved regions of E1A responsible for immortalization and transcriptional repression impaired the ability of E1A to repress ferritin H. Immunoprecipitation of ferritin in E1A transfectants demonstrated that the decrease in the ferritin H/L ratio observed at the mRNA level was also exhibited at the protein level. The E1A-dependent inhibition of ferritin H was also observed in a chimeric gene containing the ferritin H promoter ligated to the chloramphenicol acetyltransferase reporter gene, but was not observed in control genes in which chloramphenicol acetyltransferase activity was dependent on promoters derived from SV40 or the interleukin-3 gene. This suggests that E1A may repress ferritin H at the transcriptional level. These results demonstrate that the adenovirus E1A oncogene specifically modulates ferritin H expression. They also suggest that alterations in cellular iron metabolism may be among the diverse array of cellular responses induced by E1A.
Tsuji
Y
Y
Palo Alto Veterans Administration Medical Center, California 94304.
Kwak
E
E
Saika
T
T
Torti
S V
SV
Torti
F M
FM
D016475:3T3 Cells; D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005293:Ferritins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D005786:Gene Expression Regulation; D051379:Mice; D009857:Oncogenes; D014162:Transfection
D017500:Adenovirus E1A Proteins; D005293:Ferritins; D015500:Chloramphenicol O-Acetyltransferase