cAMP-dependent protein kinase is necessary for increased NF-E2.DNA complex formation during erythroleukemia cell differentiation.
Journal Article (Journal Article)
When murine erythroleukemia (MEL) cells are induced to differentiate by hexamethylene bisacetamide (HMBA), erythroid-specific genes are transcriptionally activated; however, transcriptional activation of these genes is severely impaired in cAMP-dependent protein kinase (protein kinase A)-deficient MEL cells. The transcription factor NF-E2, composed of a 45-kDa (p45) and an 18-kDa (p18) subunit, is essential for enhancer activity of the globin locus control regions (LCRs). DNA binding of NF-E2 and alpha-globin LCR enhancer activity was significantly less in HMBA-treated protein kinase A-deficient cells compared to cells containing normal protein kinase A activity; DNA binding of several other transcription factors was the same in both cell types. In parental cells, HMBA treatment and/or prolonged activation of protein kinase A increased the amount of NF-E2.DNA complexes without change in DNA binding affinity; the expression of p45 and p18 was the same under all conditions. p45 and p18 were phosphorylated by protein kinase A in vitro, but the phosphorylation did not affect NF-E2.DNA complexes, suggesting that protein kinase A regulates NF-E2.DNA complex formation indirectly, e.g. by altering expression of a regulatory factor(s). Thus, protein kinase A appears to be necessary for increased NF-E2.DNA complex formation during differentiation of MEL cells and may influence erythroid-specific gene expression through this mechanism.
Full Text
Duke Authors
Cited Authors
- Garingo, AD; Suhasini, M; Andrews, NC; Pilz, RB
Published Date
- April 21, 1995
Published In
Volume / Issue
- 270 / 16
Start / End Page
- 9169 - 9177
PubMed ID
- 7721832
International Standard Serial Number (ISSN)
- 0021-9258
Digital Object Identifier (DOI)
- 10.1074/jbc.270.16.9169
Language
- eng
Conference Location
- United States