Regulation of DeltaFosB transcriptional activity by Ser27 phosphorylation.
The transcription factor, DeltaFosB, is an important mediator of the long-term plasticity induced in brain by chronic exposure to drugs of abuse, stress, or several other psychoactive stimuli. We have previously demonstrated that the casein kinase 2 (CK2)-mediated phosphorylation of a highly conserved N-terminal serine (Ser27) plays a critical role in regulating DeltaFosB's unusual stability, while it does not affect that of the full-length FosB protein. In the present study, we analysed whether CK2 and Ser27 phosphorylation also play a role in regulating DeltaFosB's transcriptional activity. Our findings indicate that CK2 activation increases DeltaFosB's transactivation potential, while CK2 inhibition decreases it. Further, we show that preventing Ser27 phosphorylation by mutating the site to Ala results in a significant decrease in DeltaFosB transactivation, without affecting DeltaFosB's subcellular localization or DNA-binding affinity. In contrast, Ser27 does not seem to play a role in the transactivation potential of full-length FosB. These findings constitute the first evidence of a role for phosphorylation in DeltaFosB's transcriptional activity.
Ulery
Paula G
PG
Department of Psychiatry, Center for Basic Neuroscience, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas Texas, USA.
Nestler
Eric J
EJ
D000818:Animals; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015151:Immunoblotting / Q000379:methods; D016716:PC12 Cells; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D012694:Serine / Q000378:metabolism*; D013096:Spermine / Q000494:pharmacology; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*; D014162:Transfection / Q000379:methods; D000097796:Nucleolin
D047390:Casein Kinase II; D010750:Phosphoproteins; D016760:Proto-Oncogene Proteins c-fos; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D012694:Serine; D013096:Spermine; D018808:Transcription Factor AP-1; D000097796:Nucleolin