Post-transcriptional regulation of the human liver/bone/kidney alkaline phosphatase gene
Osteoblasts express high levels of liver/bone/kidney alkaline phosphatase (LBK AP), an enzyme critical for bone formation. Other tissues and cell types generally express much lower levels of LBK AP and correspondingly lower levels of mRNA. In light of our early observations that the human LBK AP pro...
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Published in | The Journal of biological chemistry Vol. 266; no. 7; pp. 4207 - 4213 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
American Society for Biochemistry and Molecular Biology
05.03.1991
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Subjects | |
Online Access | Get full text |
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Summary: | Osteoblasts express high levels of liver/bone/kidney alkaline phosphatase (LBK AP), an enzyme critical for bone formation.
Other tissues and cell types generally express much lower levels of LBK AP and correspondingly lower levels of mRNA. In light
of our early observations that the human LBK AP promoter is expressed equally when transfected into a variety of different
cells, we have carried out a detailed study of LBK AP gene expression in Saos-2 cells which are osteoblast-derived and express
high levels of LBK AP mRNA, and in HepG2 hepatoblastoma cells which express LBK AP mRNA at levels which are approximately
1000-fold lower. Our results indicate that both of these cells utilize the same promoter sequences to initiate transcription
of their LBK AP genes at roughly the same rates. Moreover, the stability of cytoplasmic LBK AP mRNA is equal in both cell
types. The lack of any apparent buildup of unspliced precursor mRNA in the nucleus of HepG2 cells leads us to the conclusion
that splicing (and nuclear export) is equivalent. It is therefore likely that differential expression is controlled at a very
early step post-transcription, possibly by sequences that destabilize the nascent RNA in HepG2 cells. We reason that these
destabilizing sequences are located in the gene's introns because a transfected LBK AP minigene, comprised of the full length
cDNA and flanking sequences, is expressed efficiently in both cell types. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/S0021-9258(20)64308-3 |