cAMP-dependent protein kinase is necessary for increased NF-E2.DNA complex formation during erythroleukemia cell differentiation.

Published

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

Pubmed Central 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