Modulation of transcription factor Sp1 by cAMP-dependent protein kinase

Transcription factor Spl is a phosphoprotein whose level and DNA binding activity are markedly increased in doxorubicin-resistant HL-60 (HL-60/AR) leukemia cells, The trans-activating and DNA binding properties of Spl in HL-60/AR cells are stimulated by cAMP-dependent protein kinase (PKA) and PKA agonists and inhibited by PKA antagonists as well as by the PKA regulatory subunit, Reporter gene activity under the control of the Spl-dependent SV40 promoter is stimulated in insect cells transiently expressing Spl and PKA, and the DNA binding activity of recombinant Spl is activated by exogenous PKA in vitro, These results indicate that Spl is a cAMP-responsive transcription factor and that Spl-dependent genes may be modulated through a cAMP-dependent signaling pathway.